96
Peritoneal Dialysis: Principles,
Techniques, and Adequacy
Peritoneal dialysis (PD) is used by approximately 200,000 end-stage
renal disease (ESRD) patients worldwide, representing approximately
7% of the total dialysis population.1 In PD the peritoneal cavity is used
as a container for 2 to 2.5 liters of sterile, usually glucose-containing,
dialysis fluid, which is exchanged four to five times daily by permanently
indwelling catheter. The dialysis fluid is provided in plastic bags. The
peritoneal membrane, via the peritoneal capillaries, acts as an endog-
enous dialyzing membrane. Across this membrane, waste products
diffuse into the dialysate and excess body fluid is removed by osmosis
induced by the glucose or another osmotic agent in the dialysis fluid
(ultrafiltration [UF]). PD is usually provided 24 h/day and 7 days/wk
in the form of continuous ambulatory peritoneal dialysis (CAPD).
Approximately one third of the patients in most centers receive auto-
mated peritoneal dialysis (APD; sometimes also referred to as continuous
cycling peritoneal dialysis [CCPD]), in which nightly exchanges are
delivered via an automatic PD cycler. The use of PD as a modality for
ESRD treatment varies widely among countries, mostly because of
nonmedical factors such as the reimbursement policy.
ADVANTAGES AND LIMITATIONS
OF PERITONEAL DIALYSIS
If patients or their caregivers are competent to undertake PD, the only
absolute contraindications are large diaphragmatic defects, excessive
peritoneal adhesions, surgically uncorrectable abdominal hernias, or
acute ischemic or infectious bowel disease. These and other relative
contraindications are discussed further in Chapter 97. PD is best used
for patients with some residual renal function, although anuric patients
may do very well. Most patients who start PD will eventually, after
several years, transfer to other modalities of renal replacement therapy
(RRT), such as hemodialysis (HD), if adequacy cannot be maintained
or as a result of other complications, such as recurrent peritonitis or
exit site or catheter problems. Only rarely do HD patients transfer to
PD, most commonly because of failure to maintain adequate vascular
access.
PD offers several advantages over HD, at least during the first 2 or
3 years of treatment. First, PD represents a slow, continuous, physiologic
mode of removal of small solutes and excess body water, associated
with relatively stable blood chemistry and body hydration status. Second,
there is no need for vascular access. The absence of vascular access and
the absence of the blood-membrane contact of HD make catabolic
stimuli less prominent in PD than in HD. Furthermore, residual renal
function is somewhat better preserved in PD patients than in HD patients.
Because of its continuous nature, PD provides a standardized weekly
†
Deceased.
Bengt Rippe †
Kt/V similar to that of thrice-weekly HD despite less efficient small-
solute clearance.
PD also has potential disadvantages, including increased workload
for patients and families, an increased risk for dyslipidemia, a relatively
high glucose load when glucose-based solutions are used, and a tendency
to mild chronic volume overload. In addition, not all patients are able
to safely perform PD, although this can be mitigated by using profes-
sional or nonprofessional dialysis assistants. The issue of dialysis modality
selection is discussed in Chapter 90.
PD is a home-based therapy, and most patients are trained to do
the exchanges themselves. In general, home dialysis patients have a
better quality of life than those on other types of dialysis. The number
of hospital visits is reduced, and the ability to travel is increased. Fur-
thermore, several studies have shown a lower incidence and severity of
delayed graft function in PD patients after transplantation.2 In children,
PD (usually APD) is the preferred dialysis modality because it is non-
invasive and socially acceptable, reducing hospital visits and allowing
the child to attend school. Advocates of PD often recommend that RRT
should ideally begin with PD according to the patient’s choice and then
proceed, as required when residual renal function declines, to HD or
transplantation. PD should thus be regarded as part of an integrated
RRT program, together with HD and transplantation.3
PRINCIPLES OF PERITONEAL DIALYSIS
Three-Pore Model
The major principles governing solute and fluid transport across the
peritoneal membrane are diffusion, driven by concentration gradients,
and convection (filtration or UF), driven by osmotic or hydrostatic
pressure gradients. The capillary wall and the interstitium together
serve to separate the plasma in the peritoneal capillaries from the fluid
in the peritoneal cavity. For the transport of fluid (UF) and large solutes,
the capillary wall is by far the dominating transport barrier. However,
for small-solute diffusion the interstitium accounts for approximately
one third of the transport (diffusion) resistance; the mesothelium lining
the peritoneal cavity is of much less significance. The permeability of
the capillary wall can be described by a three-pore model of membrane
transport (Fig. 96.1).4 In the capillary wall the major route for small-
solute and fluid exchange between the plasma and the peritoneal cavity
is the space between individual endothelial cells, the interendothelial
clefts. The functional radius of the permeable pathways in these clefts,
denoted small pores, is 40 to 50 Å, slightly larger than the radius of
albumin (36 Å). The size of these pores markedly impedes the transit
of albumin and completely prevents the passage of larger molecules
(e.g., immunoglobulins and α2-macroglobulin). However, larger proteins
can transit via very rare large pores (radius ~250 Å) in capillaries and
postcapillary venules. The large pores constitute only 0.01% of the total
1103
1104 SECTION XVIII Dialytic Therapies
Three-Pore Model
Smallest pore Small pore Large pore
(water channel) 4 nm >15 nm
<0.5 nm
Peritoneal
membrane
Water Small solute Large molecule
Fig. 96.1 Three-pore model. The small pores (4 nm) represent the
major pathway across the peritoneum through which small solutes
move by diffusion and water by convection driven by hydrostatic, colloid
osmotic, and crystalloid osmotic pressure differences. Across large pores
(>15 nm), macromolecules move out slowly by convection from plasma
to the peritoneal cavity. The smallest pores (<0.5 nm) are represented
by aquaporins permeable to water, but impermeable to solutes. Water
moves here exclusively by crystalloid osmotic pressure.
Fig. 96.2 Light microscopic section of a peritoneal membrane
with capillaries and venules (to the right) in an “amorphous”
interstitium. The peritoneum is lined by a thin layer of mesothelium
(to the left). Capillaries and venules, as well as the mesothelium, are
immunocytochemically stained for aquaporin-1 (AQP1) (brownish color).
(From reference 51.)
number of capillary pores, and the transport across them occurs by
hydrostatic pressure–driven unidirectional filtration from the plasma
to the peritoneal cavity. In addition, the capillary wall has a high per-
meability to osmotic water transport via aquaporin-1 (AQP1) channels
in the endothelial cell membranes (Fig. 96.2).5
Fluid Kinetics
Under normal (non-PD) conditions, most transport occurs via the
small pores. Only 2% of peritoneal water transport occurs via AQP1. In
PD, fluid removal is markedly enhanced by infusion of a hyperosmolar
dialysate into the peritoneal cavity. The type of osmotic agent used
markedly affects the mechanism of osmosis. Glucose will induce fluid
flow through both AQP1 (~45%) and small pores (~55%), whereas
large molecules, such as polyglucose (icodextrin) will remove fluid
mainly via small pores (~90%). Thus glucose osmosis will result in
a rapid dilution of the peritoneal dialysate, as reflected by a fall in
sodium concentration (sodium sieving) during the first 2 hours of
the dialysate dwell, caused by relatively large transport via the water-
only AQP1 channels; this tends to correct later as diffusion across the
small pores eventually increases the sodium concentration to that in
the plasma.
Glucose is usually available at three concentrations that vary
somewhat among manufacturers: low (1.36% or 1.5%), intermediate
(2.27% or 2.5%), and high (3.86% or 4.5%). Fig. 96.3A demonstrates
the intraperitoneal fluid kinetics, computer simulated using the three-
pore model, over 12 hours of dwell time with these three solutions.
Glucose is an intermediate-size osmolyte with a low osmotic efficiency
(osmotic reflection coefficient [σ] = 0.03) across small pores, whereas
glucose is 100% efficient as an osmotic agent across AQP1 (σ = 1).
For that reason, glucose will markedly (30-fold) boost the transport
of fluid through AQPs and thus redistribute fluid transport away from
the small pores toward AQP1, resulting in significant sodium sieving.
For example, for 3.86% glucose in the PD solution, the dialysate Na+
concentration will drop from 132 mmol/l to 123 mmol/l in 60 to 100
minutes, which later increases toward serum Na+ concentration (see
Fig. 96.3B). On the other hand, icodextrin, with an average molecular
weight of 17 kDa, has a high osmotic efficiency (σ ~0.5) across small
pores and in relative terms is rather inefficient across AQPs. Hence,
during icodextrin-induced osmosis only a very minor fraction of the UF
will occur through AQP1, producing insignificant sodium sieving (see
Fig. 96.4B).
In addition to the size of the osmotic agent, the degree of sodium
sieving depends on the presence and quantity of AQP1, total rate of
net UF (which is mainly determined by the glucose concentration),
and diffusion capacity of Na+. A high rate of small-solute transport
(and thereby of sodium diffusion) in fast transporters will manifest as
rapid equilibration of small solutes (creatinine and glucose) in the
peritoneal equilibration test (PET; see later) and will also reduce sodium
sieving.
In the absence of an osmotic agent in the PD fluid, the dialysate
would be reabsorbed into the plasma within a few hours, mainly driven
by the difference in colloid osmotic pressure between plasma and the
peritoneum. This absorption will to a major extent occur via small
pores, whereas approximately 30% of the peritoneal fluid will be removed
by lymphatic absorption. The partial fluid flows in the peritoneal mem-
brane modeled across different fluid conductive pathways in the three-
pore model (for 3.86% glucose) are shown in Fig. 96.5. It is the presence
of relatively high concentrations of glucose in the peritoneal fluid that
prevents the reabsorption of fluid into the plasma during the first few
hours of the dwell.
Patients who have a high rate of sodium diffusion (fast transporters)
also have rapid transport of glucose out of the peritoneal cavity. There-
fore the glucose gradient favoring UF dissipates more rapidly, and it is
harder to achieve effective fluid removal compared with “slow trans-
porters.” In fast transporters the maximum UF volume is reduced and
UF occurs earlier. There is usually also a more rapid reabsorption of
fluid in the late phase of the dwell. The mechanism of fluid loss from
the peritoneum is controversial, because some authors claim that the
peritoneal fluid loss occurring in the late phase of the PD dwell is
dominated by lymphatic absorption.6
Effective Peritoneal Surface Area
The functional surface area of the peritoneum reflects the effective
surface area of the peritoneal capillaries.7 The transport of small solutes,
such as urea, creatinine, and glucose, is partly limited by the degree of
perfusion of these capillaries—the “effective” peritoneal membrane
blood flow. Furthermore, as mentioned earlier, some of the diffusion
resistance for the smallest solutes (urea and creatinine) is located in
the interstitium. The number of effectively perfused capillaries is increased
 CHAPTER 96 Peritoneal Dialysis: Principles, Techniques, and Adequacy 1105

Ultrafiltration Volume as a Function

of Dwell Time and Glucose Concentration
800

600

400

200

UFV, mL
1.36%
0
0 60 120 180 240 300 360 420 480 540 600 660 720
-200
2.27%
-400
3.86%
-600

-800

A Time (min)

Dialysate Sodium Concentration as a Function

of Dwell Time

142
140
138
136
[Na], mmol/L

134
132
130
128
126
124

122
0 60 120 180 240 300 360 420 480 540 600 660 720
Time (min)
B
Fig. 96.3 (A) Ultrafiltration as a function of dwell time. Net ultrafiltration volume (UFV) as a function of dwell
time for 3.86% (yellow line), 2.27% (green line), and 1.36% (blue line) glucose, computer simulated using
the three-pore model of peritoneal transport. (B) Dialysate sodium as a function of dwell time. Dialysate
sodium as a function of dwell time for 3.86% (yellow line), 2.27% (green line), and 1.36% (blue line) glucose,
computer simulated according using the three-pore model of peritoneal transport.

by arteriolar vasodilation and reduced by vasoconstriction. These altera-
tions often occur without large changes in the fluid permeability (hydrau-
lic conductance [LpS]) of the peritoneum. Thus, during vasodilation
or vasoconstriction, there is usually a dissociation between changes in
the permeability–surface area product (PS) for small solutes and in the
LpS of the membrane. Vasodilation, with recruitment of capillary surface
area, occurs early in the dwell when glucose is used as the osmotic
agent, causing early, transient increases in PS.8
Peritonitis is also associated with marked vasodilation, again leading
to increases in small-solute PS, in the absence of large changes in LpS,
during the first 60 to 100 minutes of the dwell. However, in some
patients with peritonitis, an increase in LpS will result in relative increased
fluid transport across the small pores. Furthermore, there is usually an
opening of large pores in the capillaries (and postcapillary venules),
resulting in enhanced leakage of macromolecules (e.g., albumin and
immunoglobulins) from plasma to peritoneum. Peritonitis may thus
result in relative difficulty in removing fluid (because of rapid dissipa-
tion of intraperitoneal glucose), a reduced sodium sieving (because of
the reduced UF and increased Na+ diffusion), and a markedly increased
leakage of proteins to the dialysate.
The contact area between the dialysate and the peritoneal tissue
varies as a result of posture and fill volume. Adult patients usually toler-
ate 2 to 2.5 liters of instilled volume, with larger volumes typically
possible at night when the patient is supine. An intraperitoneal hydro-
static pressure (IPP) of less than 18 cm H2O (supine position) is usually
tolerated.9 At higher pressures (>18 cm H2O) the patient usually feels
some discomfort. At intraperitoneal volumes of less than 2 liters there
is a reduction in small-solute PS, whereas PS is only moderately increased
at high fill volumes. Overall, an increased fill volume implies a more
efficient exchange with regard to both small-solute exchange and UF,
the latter being much more pronounced for hypertonic solutions.10 For
a long time it was thought that increased fill volumes would directly
1106 SECTION XVIII Dialytic Therapies

Ultrafiltration Profiles for PD

800

600

UFV, mL
400

200

0
0 60 120 180 240 300 360 420 480 540 600 660 720
Time (min)
A

Sodium Sieving Curves for PD

142
140
138
136
[Na], mmol/L

134
132
130
128
126
124

122
0 60 120 180 240 300 360 420 480 540 600 660 720
Time (min)
B
Fig. 96.4 (A) Ultrafiltration (UF) profiles for peritoneal dialysis (PD). Ultrafiltration profile for 7.5% icodextrin
(blue line), computer simulated according to the three-pore model in an average patient who is not naïve to
icodextrin, in comparison with the computer-simulated UF curve for 3.86% glucose (red line). UFV, Ultrafiltra-
tion volume. (B) Sodium sieving curves for PD. Sodium-sieving curves for 7.5% icodextrin (blue line) and
3.86% glucose (red line) (see Fig. 96.3). Na, Sodium. (A from reference 10.)

affect peritoneal fluid reabsorption by the hydrostatic pressure effect
(increases in IPP). However, because 80% of any increase in IPP is
transmitted via vein compression back to the capillaries, the actual
changes in the transcapillary hydrostatic pressure gradient, which governs
UF, will be rather small.11 Thus the impact of IPP on fluid absorption
is moderate.12
PERITONEAL ACCESS
The key to successful chronic PD is a safe and permanent access to the
peritoneal cavity (Fig. 96.6). Catheter-related complications cause sig-
nificant morbidity, sometimes forcing the removal of the catheter.
Catheter-related problems are a cause of permanent transfer to HD in
up to 20% of all patients. Most catheters are derived from that originally
devised by Tenckhoff and Schechter.13 The Tenckhoff catheter is a Silastic
tube with side holes along its intraperitoneal portion. There are usually
one or two Dacron cuffs, allowing tissue ingrowth, which secures the
catheter in place and prevents pericatheter leakage and infection. The
Tenckhoff catheter is straight, having one cuff lying on the peritoneum
with the catheter tip pointing in the caudal direction; the outer cuff is
close to the skin exit. Several centimeters of the catheter is thus located
transcutaneously. Intraperitoneal and transcutaneous catheter modifica-
tions continue to appear, indicating that no single design is perfect (Fig.
96.7). Although several studies report less frequent catheter drainage
failures with use of the arcuate “swan neck” catheter (see Fig. 96.7)
compared with straight catheters, there is no hard evidence that any of
the modified catheters on the market are actually superior to the original
(one- or two-cuff) Tenckhoff catheter.14
Ideally, catheters should be inserted in the operating room under
sterile conditions by an experienced and appropriately trained operator.
Presurgical assessment for the presence of herniation or any weakness
of the abdominal wall is essential. If present, it may be possible to
correct these at the time of catheter insertion. Before the operation,
eradication of nasal carriage of Staphylococcus aureus with locally applied
antibacterial agents (such as mupirocin) significantly reduces exit site
infection rates. A single preoperative intravenous dose of a first- or
second-generation cephalosporin is also recommended. To avoid devel-
opment of vancomycin-resistant enterococcus, vancomycin should not
be used as a prophylactic agent. Several placement techniques have
been described and practiced: surgical mini-laparotomy and dissection,
 CHAPTER 96 Peritoneal Dialysis: Principles, Techniques, and Adequacy
Peritoneal Volume Flows as a
Function of Dwell Time
7
6 Small pores
5 Aquaporins
4
Flow (ml/min)
Large pores
3 Lymph flow
2
1 2 cuff coil catheter
0
!1 0 120 240 360 480 600 720
!2
Time (min)
Fig. 96.5 Peritoneal volume flows as a function of dwell time.
Peritoneal volume flows as a function of dwell time for 3.86% glucose
partitioned among aquaporins, small pores, large pores, and lymphatic
absorption. The small-pore volume flow is initially approximately 60%
of total volume flow and becomes negative after peak time (220 min).
The aquaporin-mediated water flow becomes slightly negative after
approximately 250 min. The large-pore volume flow is negligible and
remains constant throughout the dwell, as does lymphatic absorption
(0.3 ml/min). (Modified from reference 52.)
Fig. 96.6 A recently implanted peritoneal dialysis catheter in
situ. Note the subumbilical midline scar where the catheter enters the
peritoneal cavity (arrow).
blind placement using the Tenckhoff trocar, blind placement using a
guidewire (Seldinger technique), mini-trocar peritoneoscopy placement,
and laparoscopy. These techniques are discussed further in Chapter 92.
TECHNIQUES OF PERITONEAL DIALYSIS
In CAPD, 2 to 2.5 liters of dialysis fluid is instilled into the peritoneal
cavity four or five times daily. In 4 to 5 hours there is 95% equilibration
of urea and approximately 65% equilibration of creatinine, whereas
the glucose gradient has dissipated to approximately 40% of the initial
value. For glucose as an osmotic agent, 4 to 5 hours is a suitable dwell
time. For night dwell exchanges, longer dwell times can be accepted (8
to 10 hours). Furthermore, there is room for individual exchange sched-
ules that can be adjusted to suit individual patient convenience. Dwell
times shorter than 4 to 5 hours can be performed with use of a machine
(cycler). This technique can be used to maintain adequate dialysis when
1107
Common Types of Peritoneal
Dialysis Catheter
Straight 1 cuff catheter
Straight 2 cuff catheter
Swan neck catheter
Toronto Western catheter
Fig. 96.7 Common types of peritoneal dialysis catheter.
more frequent, lower volume exchanges are needed—for example, to
minimize leakage in conjunction with catheter insertion, hernia repair,
or abdominal operations. Rapid exchanges also may be required during
treatment for peritonitis or in patients with fluid overload when the
patient’s hydration status needs to be corrected rapidly.
Today, double-bag systems (so-called Y systems) are in general use
according to the principle “flush before fill.” The double-bag system
contains the unused dialysis fluid connected to an empty sterile drain
bag via a Y-set tubing system. After the patient has connected the system
and flushed the connection (for 2 to 3 seconds), a frangible (breakable)
pin to the drain bag is opened, and the peritoneal cavity is drained over
10 to 15 minutes to fill the drain bag. Then this bag is clamped, and
the fresh bag opened, to fill the peritoneal cavity over another 10 to 15
minutes. The time for exchange (instillation and drainage), if the catheter
is in good order, should not exceed a total of 30 minutes. Usually the
first 1.6 to 1.8 liters will drain rapidly (at ≥200 ml/min), whereas the
last 200 to 300 ml will drain much more slowly. The breakpoint between
the rapid and the slow phase may vary markedly from individual to
individual.
APD is usually performed with use of a cycler overnight (8 to 10
hours), during which large volumes (10 to 20 liters) can be exchanged.
During daytime the APD patient usually has a so-called wet day—that
is, a long dwell, usually with icodextrin as the osmotic agent in the
dialysis fluid. Some patients with nightly APD perform one daily exchange
so that there are two long (6 to 8 hours) daily dwells. Most cyclers can
be programmed to vary inflow volume, inflow time, dwell time, and
drain time. Cyclers usually warm the fluid before inflow, and they also
monitor outflow volume and the excess drainage (UF volume). Current
APD machines have alarms for inflow failure, overheating, and poor
drainage. Some cyclers interrupt drainage at the breakpoint between
the fast and slow phases to make the exchange more efficient. Another
way to accelerate exchanges is to allow a considerable sump volume in
the peritoneal cavity by not letting all the fluid drain; subsequent inflow
volumes are proportionally reduced, and after multiple cycles complete
drainage occurs. This technique is called tidal peritoneal dialysis (TPD).
The exchange volume should be adjusted according to the patient’s
size. Adult patients weighing less than 60 kg should start with 1.5-liter
1108 SECTION XVIII Dialytic Therapies
bags. The average patient (60 to 80 kg) should receive 2-liter exchanges,
and for patients weighing more than 80 kg, 2.5 liters should be used.
If pressure monitoring systems are available, the IPP may inform the
choice of exchange volume. In the supine position, most patients have
an IPP of 12 cm H2O.
PERITONEAL DIALYSIS FLUIDS
The majority of PD fluids used today have the composition of a lactate-
buffered, balanced salt solution devoid of potassium, with glucose (1.36%
or 1.5%, 2.27% or 2.5%, 3.86% or 4.5%) as the osmotic agent. The
K+ concentration in PD fluids is zero to aid control of potassium
balance.
Lactate is used as a buffer instead of bicarbonate, because bicarbon-
ate and Ca2+ may precipitate (to form calcium carbonate) during storage.
With the advent of newer multichambered PD delivery systems, it is
possible to replace lactate with bicarbonate and make a number of
other solution modifications that previously were not feasible. However,
the higher cost of the newer more physiologic fluid formulations should
be borne in mind. For example, in the United Kingdom, icodextrin
solution costs approximately 80% more per unit volume than glucose-
based solutions.
Electrolyte Concentration
In current PD fluids the concentrations of Na+, Cl−, Ca2+, and Mg2+ are
selected to be close to the serum concentration. The removal of these
ions across the peritoneum is therefore a result of the low diffusion
gradient, more or less completely dependent on convection. For every
deciliter of fluid removed in a 4-hour dwell, approximately 10 mmol
of Na+15 and 0.1 mmol of Ca2+ are removed, provided that serum Na+
and Ca2+ are within the reference ranges.11
The frequent use of calcium-containing phosphate binders requires
an understanding of Ca2+ kinetics for various types of dialysis fluids to
avoid hypercalcemia. The calcium concentration of current PD solu-
tions is usually 1.25 to 1.75 mmol/l. However, because Ca2+, like Na+
and Mg2+, has a UF-dominated transport, 1.25 mmol/l may be considered
appropriate only for 1.36% glucose, to achieve a zero (neutral) peritoneal
calcium removal. For example, UF-driven Ca2+ loss will occur during
a 4-hour dwell with 3.86% glucose solution. With use of a three-
compartment system for the PD bags, it would be possible to adapt the
dialysis fluid Ca2+ concentration to obtain net zero peritoneal Ca2+
transport across the peritoneum, or to reach a preset calcium removal
target, for each PD fluid glucose concentration used.16 However, in
currently available PD solutions, Ca2+ concentration is not variable as
a function of glucose concentration; therefore 1.25 mmol/l Ca2+ is rec-
ommended when patients use calcium-containing phosphate binders.
It should be noted that net peritoneal calcium removal with 1.25 mmol/l
Ca2+ level can be achieved only by PD fluids containing 2.27% or 3.86%
glucose.
The Mg2+ concentration commonly used in current PD solutions is
0.25 to 0.75 mmol/l. For 1.36% glucose, 0.25 mmol/l would be appro-
priate for zero Mg2+ transport during the dwell, whereas for higher
dialysis fluid glucose concentrations there will be net Mg2+ losses.
Osmotic Agents
Glucose is the principal osmotic agent used for fluid removal (UF) in
PD. Alternative commercially available osmotic agents are amino acids
and icodextrin. Icodextrin is a polydisperse glucose polymer with an
average molecular weight of 17 kDa.17 However, because of the poly-
dispersity of icodextrin, approximately 70% of the molecules have a
molecular weight of 3 kDa or less.10 Icodextrin is available as a 7.5%
solution with essentially the same electrolyte composition as glucose-
based dialysates. The osmolality of the glucose polymer solution, unlike
that of 1.36% glucose (osmolality 350 mOsm/kg) dialysis fluid, is within
the same range, or actually slightly lower, than that of normal serum.
The presence of larger molecules in the icodextrin solution, compared
with those in glucose-based solutions, improves the osmotic efficiency
markedly across the small pores (σ = 0.5) and also reduces dissipation
of the osmotic gradient over time. This yields a sustained UF over 8 to
12 hours (see Fig. 96.4A). Therefore icodextrin is preferable for long
dwell exchanges, for example, overnight, and particularly for patients
who tend to absorb glucose rapidly (fast transporters, see later). Ico-
dextrin is slowly absorbed into serum and degraded (circulating
α-amylase) to oligosaccharides, such as maltose, which may give false-
positive results for glucose, leading to erroneous measures of hyper-
glycemia and inappropriate use of glucose-lowering agents.18
Another alternative osmotic agent that is commercially available is
a 1.1% amino acid mixture having the same osmolality as 1.36% glucose.19
According to some studies, regular use of this dialysate may increase
certain nutritional indices, although there is also some evidence that
amino acid solutions increase acidosis and raise plasma urea. Both
icodextrin-based and amino acid–based solutions may be used to reduce
the glucose exposure of the peritoneal membrane and total glucose
load to the patient.
Until recently, conventional PD solutions have had a low pH and a
high concentration of glucose degradation products (GDPs). GDPs are
reactive carbonyl compounds that form during heat sterilization and/
or storage of glucose-based solutions. GDPs are toxic to a variety of
cells in vitro and also potentially toxic in vivo.20 By the use of multi-
compartment systems reconstituted immediately before infusion, it has
been possible to compose new solutions with much lower concentrations
of GDPs and a neutral pH and also to use bicarbonate or bicarbonate-
lactate mixtures as buffers.21-23 Solutions using bicarbonate or bicarbonate-
lactate mixtures result in significantly less infusion pain and are as
effective as lactate at correcting acidosis, when used at the same total
buffer ion concentration.24 In prospective, randomized studies these
fluids have been associated with improvement in dialysate effluent
markers of peritoneal membrane integrity, particularly cancer antigen
125 (CA-125), a measure of peritoneal mesothelial cell mass.21-23 There
also have been some indications of improved residual renal function
in patients with PD solutions low in GDPs,23 although this was not
confirmed in recent prospective, randomized studies.25,26 One of those
studies, however, the balANZ study,26 suggested that biocompatible PD
solutions may delay the onset of anuria and reduce the incidence of
peritonitis compared with conventional solutions.
ASSESSMENTS OF PERITONEAL SOLUTE
TRANSPORT AND ULTRAFILTRATION
Small-Solute Removal
The net removal of solutes and fluid during PD, in excess of residual
renal excretion, can be measured by evaluating the drained dialysate.
For this purpose the concentrations of urea and creatinine are measured
in dialysate and plasma. The dialysate-plasma concentration ratios (D/P)
of either of these solutes multiplied by the daily drain volume gives the
24-hour clearance. Weekly creatinine and urea clearances are obtained
by multiplying these figures by 7. For comparison among patients,
creatinine clearance is conventionally standardized to body standard
surface area (1.73 m2), and urea clearance (mostly for comparison with
HD) is expressed as Kt/V (where Kt is the weekly clearance and V the
volume of distribution of urea). In PD, routine assessment of V is
imprecise, in contrast to the situation in HD, in which V can be math-
ematically derived directly from urea kinetics. V should preferably be
determined by direct techniques, such as from the dilution of isotopic
 CHAPTER 96 Peritoneal Dialysis: Principles, Techniques, and Adequacy
water (total body water); in practice, however, V is usually approximated
from standard tables using BW and height as anthropometric parameters
together with gender.27 Criticism of the Kt/V concept in PD is based
on the uncertainty of determining a correct value for V. In those who
are markedly underweight or overweight the ideal body weight should
be used for calculating V.28
Large-Solute Removal
For more insight into peritoneal transport, the clearance of larger solutes
such as β2-microglobulin, as well as markers for transport across the
large pores, such as albumin, immunoglobulins and α2-macroglobulin,
can be measured. Although many centers assess the daily peritoneal
removal of total protein and/or albumin, measurements of most other
solutes are not made in routine clinical practice.
Ultrafiltration
UF can be assessed with a 24-hour collection. Even if done accurately,
there is a considerable dwell-to-dwell and day-to-day variability in UF
depending on drainage conditions, posture, and varying levels of residual
(sump) intraperitoneal volume. Reasonably accurate estimations of
daily UF volume can be obtained by averaging collections of all fluid
over a period of several days. In clinical practice, the patient’s own daily
dialysis records also should be examined with respect to dwell-to-dwell
UF volumes and the number of hypertonic bags used per day. For a
3.86% glucose dwell a UF volume less than 400 ml will indicate insuf-
ficient UF—that is, ultrafiltration failure (UFF). UF volume also can
be determined by the PET, as described later. In a routine 2.27% glucose
PET, less than 200 ml of UF in 4 hours signals UFF. More accurate
determination of intraperitoneal volume can be achieved as a function
of time with use of a marker, such as iodine-125 (125I)–human serum
albumin or dextran 70. This is not required in routine clinical practice
but as a research tool allows more precise UF volume estimations.
Peritoneal Membrane Function
Peritoneal Equilibration Test
The PET yields approximate estimations of the rate of peritoneal trans-
port of small solutes and of UF capacity.9 The rate of small-solute
transport depends on the effective peritoneal surface area, which is
essentially dependent on the number of effectively perfused capillaries
available for exchange (and the blood flow). The volume ultrafiltered
in 4 hours is a function of the osmotic conductance to glucose (OCg;
the peritoneal UF coefficient multiplied by the reflection coefficient for
glucose) and the rate of dissipation of the glucose osmotic gradient
(the rate of small-solute transport). In general, when the rate of glucose
disappearance is high, UF volume is low.
The PET procedure is summarized in Box 96.1. After an overnight
dwell (8 to 12 hours) the dialysate fluid is drained, and a 2-liter 2.27%
glucose bag is infused for 10 minutes with the patient in the supine
position (rolling from side to side every 2 minutes). After 10 minutes—
that is, at completion of the infusion—200 ml is drained into the drain-
age bag and mixed, and a zero time dialysate sample taken. At the end
of the 4-hour dwell period, dialysate is drained out and measured. The
net volume is noted. Concentrations of glucose and creatinine in the
outflow and plasma are measured, as well as the concentration of glucose
in the zero sample. The results are expressed as the dialysate-plasma
(D/P) solute concentration ratio and as the dialysate glucose at 4 hours–
dialysate glucose at time zero (D/D0) concentration ratio. The higher
the D/P ratio for creatinine, the faster the rate of transport for small
solutes. According to D/P ratios for creatinine or D/D0 for glucose,
patients can be divided into slow, slow average, fast average, or fast
transporters (Fig. 96.8); transport status remains stable in approximately
70% of patients at 1 year and approximately half of patients at 2 years.
1109
BOX 96.1 Peritoneal Equilibration Test
1. Two liters (warm) 2.27% fluid instilled for 10 minutes with the patient
supine and rolling from side to side every 2 minutes.
2. Exactly at 10 minutes after start of the infusion, 200 ml is drained into the
bag. Draw 5 ml (discard); the next 5 ml taken for creatinine and glucose
determination.
3. After 2 hours, new samples collected as in 3.
4. After 4 hours (exactly), collect drainage over 20 minutes. Note total bag
weight. Subtract empty bag weight. Take samples (after mixing) for creatinine
and glucose.
5. Glucose D/D0 (the ratio of dialysate glucose at 4 hours and at time zero)
and creatinine D/P (the ration of dialysate and serum creatinine at 4 hours)
are plotted versus time (as shown in Fig. 96.8). Record the total drain
volume.
The night bag (8 to 12 hours) must be 1.36% or 2.27% glucose,
drained for 20 minutes with patient sitting.
It should, however, be emphasized that D/P measurements give only
an approximate estimation of small-solute transport rate. Additional
information can be obtained by variations, including the modified PET
(instilling a 3.86% solution and draining after 4 hours),30 the mini-PET
(instilling a 3.86% solution and draining after 1 hour), and the double–
mini-PET (instilling sequentially a 1.36% solution and a 3.86% solution,
draining each after 1 hour).
Mini–Peritoneal Equilibration Test
In the mini-PET, a 3.86% glucose solution is instilled and completely
drained after 1 hour. The Na+ concentration in the drained dialysate
assesses the degree of sodium sieving and hence gives a measure of
AQP-mediated (“free”) water flow.31,32 The fraction of “free” water
transport can be evaluated in the early phase of the dwell from the
1-hour drained volume minus the 1-hour peritoneal Na+ clearance (i.e.,
the drained Na+ – the instilled Na+ ÷ the serum Na+ concentration). In
the first hour when Na+ diffusion is negligible, the peritoneal clearance
of sodium (across small pores) will directly reflect the peritoneal small-
pore fluid clearance (UF). This value is then subtracted from the total
(1-hour) UF volume to yield an estimate of the free (AQP-mediated)
water transport. Reductions in this parameter usually occur over time
on PD, and marked reductions in free water transport are assumed to
reflect peritoneal fibrosis.33,34
Double–Mini–Peritoneal Equilibration Test
The OCg can be measured with a double–mini-PET—that is, a 1-hour
dwell with 1.36% glucose and also a 1-hour dwell with 3.86% glucose
solution. The calculation of OCg is based on the difference in the 1-hour
drained volume between the 3.86% and 1.36% glucose solutions.35 In
long-term PD, increases in D/P-creatinine and reductions in D/D0-glucose
are usually seen, eventually resulting in UFF. These changes are often
combined with moderate reductions in OCg, the latter perhaps coupled
with peritoneal fibrosis.36 Marked reductions in OCg may signal immi-
nent development of peritoneal sclerosis.37
Residual Renal Function
In PD, residual renal function is important for patient and technique
survival. Residual renal function is somewhat better preserved over
treatment time in PD than in HD.38 Residual renal function can be
assessed by collecting all urine over a day and assessing the urine con-
centrations of urea and creatinine and total urine volume. Because
renal creatinine clearance, as a result of tubular secretion, yields an
1110 SECTION XVIII Dialytic Therapies

Interpretation of Peritoneal Equilibrium Test Results

1.1 1.1
1.0 1.0 1.03

0.9 0.9
0.8 0.8 0.81

Creatinine (D/P)
Glucose (D/D0)
0.7 0.7
0.65
0.6 0.61 0.6
0.5 0.5 0.50
0.49
0.4 0.4
0.38 0.34
0.3 0.3
0.26
0.2 0.2
0.1 0.12 0.1
0 Fast 0
Fast average
0 2 4 Slow average 0 2 4
Time (h) Time (h)
Slow
Fig. 96.8 Interpretation of peritoneal equilibration test (PET) results. Changes in solute concentration
during a PET allow classification into different transport types. (Modified from reference 29.)

overestimate of the glomerular filtration rate (GFR) (by 1 to 2 ml/min) TABLE 96.1 Criteria for Peritoneal
when the GFR is 10 ml/min or lower, and renal urea clearance yields
Dialysis Adequacy Criteria for Peritoneal
an underestimate of GFR (by 1 to 2 ml/min) in the same interval of
(reduced) GFR, a good estimate of actual GFR can be calculated as the
Dialysis Adequacy
average of renal creatinine clearance and urea clearance. However, if Clinical Patient feels well and has stable lean body mass
the daily urine volume is less than 200 ml, residual renal function will No symptoms of anorexia, asthenia, nausea,
be too small to be measured accurately. emesis, insomnia
Stable nerve conductance velocity
ADEQUACY Small-solute clearance Weekly Kt/V urea >1.7 (renal + peritoneal)
Weekly creatinine clearance >50 l/1.73 m2
The most important measure of dialysis adequacy is the general clinical
Large-solute clearance Albumin clearance <0.15 ml/min
state of the patient, as manifested by a good nutritional status (main-
tained muscle mass) and the absence of anemia, edema, hypertension, Fluid balance No edema
electrolyte and acid-base disturbances, neurologic symptoms, pruritus, No hypertension
and insomnia. Management of anemia and bone disease in ESRD patients No postural hypotension
is discussed in Chapters 82 and 84, respectively. Some criteria for PD Electrolyte balance Serum potassium <5 mmol/l
adequacy are given in Table 96.1. Acid-base balance Serum bicarbonate >24 mmol/l
Nutrition Daily protein intake ≥1.2 g/kg
Small-Solute Clearance Daily calorie intake >35 kcal/kg/day
Few prospective randomized studies define adequate PD. From a clinical Serum albumin >3.5 g/l
point of view it hasbeen suggested that a weekly Kt/V above 1.7 and a BMI 20-30 kg/m2
weekly creatinine clearance above 50 l/1.73 m2 would be (minimally) Stable midarm muscle circumference
adequate for patients on CAPD. In a large prospective study (CANUSA),
the outcome for a cohort of 680 patients starting CAPD was studied BMI, Body mass index.
with an average follow-up of 2 years.39 Patients who maintained a high
Kt/V or creatinine clearance over time did better than those who did
not. An increase of 0.1 unit of Kt/V (peritoneal + renal) per week was Kt/V of 2.12 (intervention group) compared with a clearance above 50
associated with a 5% decrease in relative risk for death, and an increase l/1.73 m2 at an average peritoneal Kt/V of 1.56 (control group). However,
of 5 l/1.73 m2 of creatinine clearance per week (peritoneal + renal) was although overall mortality, hospitalization, withdrawal, and technique
associated with a 7% decrease in the relative risk for death. Further survival were similar in the two groups, the causes of withdrawal were
analysis of the CANUSA study findings indicated that the survival different. Relatively more patients in the control group withdrew because
advantage of patients with higher total small-solute clearance was entirely of uremia, hyperkalemia, and acidosis and died from congestive heart
attributed to the residual renal function. For each increase of 250 ml failure than in the intervention group.
of urine output per day, there was a 36% decrease in the relative risk From these studies it seems that renal and peritoneal clearance are
for death. In the Adequacy of Peritoneal Dialysis in Mexico (ADEMEX) not mutually comparable. High residual renal function is of greater
study,40 a large randomized controlled trial (RCT) designed to test the survival advantage than high peritoneal solute transport capacity. The
value of increasing peritoneal small-solute clearance, there was no sur- fact that the survival of PD patients is equal to or supersedes that of
vival advantage of increasing the peritoneal clearance to obtain a total HD patients during the first 2 to 3 years of dialysis (see later), despite
weekly creatinine clearance above 60 l/1.73 m2 at an average peritoneal the fact that PD provides approximately 50% of the total Kt/V of HD,
 CHAPTER 96 Peritoneal Dialysis: Principles, Techniques, and Adequacy 1111

indicates that the benefit of PD goes beyond the clearance of small survival. It seems evident that after 2 or 3 years of PD, when residual
solutes. In a European multicenter study of APD, the European Auto- renal function is low, most patients on PD are fluid overloaded.42,43 It
mated Peritoneal Dialysis Outcomes Study (EAPOS), small-solute clear- is likely that volume overload not only aggravates hypertension but
ance did not correlate with survival in anuric patients.37 On the contrary, also leads to progression of left ventricular hypertrophy, often already
total volume removal and hydration state were important factors. present at the start of PD. However, during the first year of PD there
Still, there is reasonably good evidence that a weekly Kt/V above 1.7 is often a fall in blood pressure (BP) and a reduced need for antihy-
and a weekly creatinine clearance above 50 l/1.73 m2 are adequacy pertensive agents. Unfortunately, with time on PD, BP usually rises and
targets that should be reached and maintained in a majority of patients. the number of antihypertensive drugs needed usually again increases.44
Lower values of Kt/V and creatinine clearance have been found to be In patients with evidence of volume overload, PET tests can clarify the
associated with more clinical problems and higher consumption of mechanism and guide adjustments to the dialysis regimen, if required.
erythropoiesis-stimulating agents in a large RCT. 41 Therefore it is advisable to regularly assess dialytic fluid removal in
Commercially available computer programs can predict urea and such patients over time, at least every 6 months, with a modified PET
creatinine clearances and peritoneal UF performance and provide sug- (4-hour 3.86% glucose dwell, in conjunction with a standard 2.27%
gestions for treatment options, based on drained volumes and on plasma 4-hour PET).
and dialysate creatinine and urea values. These parameters are often
obtained by PET or standardized schedules for specified dwell exchanges. Management of Fluid Overload
Some of the programs yield an estimate of peritoneal albumin clear- As total urinary water (and sodium) excretion and peritoneal UF volume
ance, which to a great extent depends on the filtration occurring across decline, it is advisable to instruct patients to restrict salt and water
large pores, being increased in “inflammation.” Recommended dialysis intake. In view of the difficulty in compliance with salt restriction, the
schedules based on the categorization of the PET are given in Table 96.2. use of PD solutions with lower sodium concentration has been advo-
cated. Preliminary studies of low-sodium PD solutions have been prom-
Fluid Balance ising with regard to reducing the need for BP-lowering drugs to control
As in all types of RRT, long-term maintenance of adequate fluid and hypertension45; however, low-sodium solutions are not yet commercially
electrolyte balance is crucial for the survival of patients on PD. As available. Loop diuretics such as furosemide 250 to 500 mg/day can be
already mentioned, the outcome of PD is directly related to residual used to maintain urine volumes but do not maintain renal clearance.
renal function, particularly a high urine output. Furthermore, patients If salt and water restriction and diuretics are not effective in maintain-
with fast transport in the PET (a more rapid absorption of glucose and ing UF, it can be enhanced by increasing the dialysis glucose concentra-
a more rapid loss of the osmotic gradient) have a reduced technique tion. Patients with alterations in peritoneal membrane function, appearing
over the first few years of PD, usually have increased small-solute trans-
port combined with only a moderate change in peritoneal UF capacity,36
and there is an increased reabsorption of fluid in the late phase of the
TABLE 96.2 Typical Peritoneal Dialysis dwell. These patients can benefit from switching to APD and the use
Regimens Required for Achievement of of icodextrin for one of the (daily) exchanges. RCTs using icodextrin
Adequate Solute Clearances for the long daytime dwell in APD have demonstrated an improved
UF and a reduced extracellular fluid volume.46 Patients who have been
PERITONEAL SOLUTE TRANSPORT
on PD for several years may have a reduced UF capacity (reduced
CHARACTERISTICS: D/P CREATININE
OCg).35,36 These patients would (theoretically) benefit less from switch-
AT 4 HOURS
ing to icodextrin because of the reduced UF capacity.10
Patient Slow
Body Average Fast Nutrition
Surface Slow (0.5 to Average Fast During their first year of treatment, CAPD patients typically have evidence
Area (m2) (<0.5) <0.65) (0.65-0.82) (>0.83) of net anabolism; the average weight gain may exceed 5 kg without any
<1.7 CAPD/APD CAPD/APD+ APD+* APD* clinical signs of fluid overload. Contributing to this weight gain is the
10-12.5 l 10-12.5 l 10-12.5 l 10-12.5 l peritoneal glucose reabsorption (on average 100 to 150 g/day), which
adds 400 to 600 kcal of energy intake daily and results in metabolic
1.7-2.0 CAPD+/APD APD+ APD+* APD+*
syndrome in approximately 50% of prevalent PD patients.47 As residual
12.5-15 l 12.5-15 l 12.5-15 l 12.5-15 l
renal function declines, the nutritional and metabolic abnormalities
>2.0 CAPD+, HD APD+ APD+* APD+* in CAPD become increasingly manifest, with reductions in lean body
15-20 l 15-20 l 15-20 l mass. The main cause of protein-energy malnutrition and wasting,
*The use of glucose polymer (icodextrin) solution for the long apart from poor food intake, is the impaired metabolism of protein
exchange will enhance both solute clearance and ultrafiltration. and energy in uremia. Despite glucose absorption, many patients on
Typical peritoneal dialysis regimens required to achieve adequate long-term CAPD have signs of energy malnutrition, a major component
solute clearance according to patient size and membrane of the uremic wasting syndrome. Contributing factors are (low-grade)
characteristics in anuric patients. The total volume of dialysate fluid inflammation associated with carbonyl and oxidative stress and with
required increases with body size, with use of 2.5- or even 3.0-liter accelerated atherosclerosis, the malnutrition inflammation atheroscle-
exchanges. As solute transport increases, the use of automated rosis syndrome.48 It is important that CAPD patients be prescribed an
peritoneal dialysis (APD) with shorter overnight exchanges is favored
adequate amount of protein (>1.2 g protein/kg/day) and energy (total
over continuous ambulatory peritoneal dialysis (CAPD). Both CAPD
and APD may have to be augmented by the use of an additional
energy intake >35 kcal/kg/day) and a sufficient dose of dialysis, enabling
exchange (denoted by +); This is given by way of an additional the patient to ingest this diet. It should be noted that the daily losses of
afternoon exchange in CAPD patients or by use of an exchange protein to the dialysate are not negligible, but approximately 5 to 7 g
device that delivers a single additional exchange at night. daily, of which approximately 4 to 5 g is albumin. This is comparable
D/P, Dialysate-plasma concentration ratios; HD, hemodialysis. to the losses occurring in nephrotic range proteinuria. The nutritional
1112 SECTION XVIII Dialytic Therapies
management of PD patients should include frequent assessments of their
nutritional status, and, if inadequate, referral for HD (or transplanta-
tion) should be considered. Nutrition in dialysis patients is discussed
further in Chapter 86.
OUTCOME OF PERITONEAL DIALYSIS
Registry data have indicated a lower risk for death in patients treated
with PD during the first 3 years of treatment compared with those
treated with HD, although overall the mortality of patients on PD
compared with HD is not significantly different.49 Survival differences
seem to vary substantially according to the underlying cause of ESRD,
age, and baseline comorbidity. In a study based on U.S. Medicare registry
data,50 HD was associated with a higher risk for death among diabetic
patients with no comorbidity and among younger patients (age 18 to
44), whereas PD was associated with a higher risk for death among
patients aged 45 to 64. In patients with mortality rates adjusted for
comorbidity at start of dialysis, there were no differences between HD
and PD among nondiabetic patients and among younger diabetic patients
(ages 18 to 44), but mortality was higher on PD for older diabetic
patients with baseline comorbidity. Limited data address comparative
survival for HD versus PD in patients older than 70, but small studies
from the NTDS study (in the United Kingdom) and the REIN study
(in France) suggest that the risk for serious outcomes such as hospi-
talization and death are similar, regardless of the modality selected. In
summary, it appears that dialysis modality does not substantially affect
major adverse clinical outcomes, provided patients are appropriately
selected.
REFERENCES
1. United States Renal Data System: Available at: http://www.usrds.org.
Accessed September 23, 2015.
2. Bleyer AJ, Burkart JM, Russell GB, et al. Dialysis modality and delayed
graft function after cadaveric renal transplantation. J Am Soc Nephrol.
1999;10:154–159.
3. Coles GA, Williams JD. What is the place of peritoneal dialysis in
the integrated treatment of renal failure? Kidney Int. 1998;54:
2234–2240.
4. Rippe B, Stelin G, Haraldsson B. Computer simulations of peritoneal
fluid transport in CAPD. Kidney Int. 1991;40:315–325.
5. Ni J, Verbavatz JM, Rippe A, et al. Aquaporin-1 plays an essential role in
water permeability and ultrafiltration during peritoneal dialysis. Kidney
Int. 2006;69:1518–1525.
6. Krediet RT. The effective lymphatic absorption rate is an accurate and
useful concept in the physiology of peritoneal dialysis. Perit Dial Int.
2004;24:309–313, discussion 316–307.
7. Flessner MF. Peritoneal transport physiology: insights from basic
research. J Am Soc Nephrol. 1991;2:122–135.
8. Waniewski J, Heimbürger O, Werynski A, et al. Diffusive mass transport
coefficients are not constant during a single exchange in continuous
ambulatory peritoneal dialysis. ASAIO J. 1996;42:M518–M523.
9. Fischbach M, Dheu C. Hydrostatic intraperitoneal pressure: an objective
tool for analyzing individual tolerance of intraperitoneal volume. Perit
Dial Int. 2005;25:338–339.
10. Rippe B, Levin L. Computer simulations of ultrafiltration profiles for
an icodextrin-based peritoneal fluid in CAPD. Kidney Int. 2000;57:
2546–2556.
11. Rippe B, Venturoli D, Simonsen O, et al. Fluid and electrolyte transport
across the peritoneal membrane during CAPD. Perit Dial Int. 2004;1:
10–27.
12. Rippe B. Is intraperitoneal pressure important? Perit Dial Int. 2006;26:
317–319, discussion 411.
13. Tenckhoff H, Schechter H. A bacteriologically safe peritoneal access
device. Trans Am Soc Artif Intern Organs. 1973;10:363–370.
14. Flanigan M, Gokal R. Peritoneal catheters and exit-site practices toward
optimum peritoneal access: a review of current developments. Perit Dial
Int. 2005;25:132–139.
15. Heimbürger O, Waniewski J, Werynski A, et al. A quantitative description
of solute and fluid transport during peritoneal dialysis. Kidney Int.
1992;41:1320–1332.
16. Simonsen O, Wieslander A, Venturoli D, et al. Mass transfer of calcium
across the peritoneum at three different peritoneal dialysis fluid Ca and
glucose concentrations. Kidney Int. 2003;64:208–215.
17. Mistry CD, Gokal R, Peers E. A randomized multicenter clinical trial
comparing isosmolar icodextrin with hyperosmolar glucose solutions in
CAPD. MIDAS Study Group. Multicenter Investigation of Icodextrin in
Ambulatory Peritoneal Dialysis. Kidney Int. 1994;46:496–503.
18. Oyibo SO, Pritchard GM, McLay L, et al. Blood glucose overestimation in
diabetic patients on continuous ambulatory peritoneal dialysis for
end-stage renal disease. Diabet Med. 2002;19:693–696.
19. Kopple JD, Bernard D, Messana J, et al. Treatment of malnourished
CAPD patients with an amino acid based dialysate. Kidney Int. 1995;47:
1148–1157.
20. Wieslander AP, Nordin MK, Kjellstrand PT, et al. Toxicity of peritoneal
dialysis fluids on cultured fibroblasts, L-929. Kidney Int. 1991;40:77–79.
21. Rippe B, Simonsen O, Heimbürger O, et al. Long-term clinical effects of a
peritoneal dialysis fluid with less glucose degradation products. Kidney
Int. 2001;59:348–357.
22. Jones S, Holmes CJ, Krediet RT, et al. Bicarbonate/lactate-based
peritoneal dialysis solution increases cancer antigen 125 and decreases
hyaluronic acid levels. Kidney Int. 2001;59:1529–1538.
23. Williams JD, Topley N, Craig KJ, et al. The Euro-Balance Trial: the effect
of a new biocompatible peritoneal dialysis fluid (balance) on the
peritoneal membrane. Kidney Int. 2004;66:408–418.
24. Mactier RA, Sprosen TS, Gokal R. Bicarbonate and bicarbonate/lactate
peritoneal dialysis solutions for the treatment of infusion pain. Kidney
Int. 1998;53:1061–1067.
25. Fan SL, Pile T, Punzalan S, et al. Randomized controlled study of
biocompatible peritoneal dialysis solutions: effect on residual renal
function. Kidney Int. 2008;73:200–206.
26. Johnson DW, Brown FG, Clarke M, et al. Effects of biocompatible versus
standard fluid on peritoneal dialysis outcomes. J Am Soc Nephrol. 2012;
23:1097–1107.
27. Watson PE, Watson ID, Batt RD. Total body water volumes for adult
males and females estimated from simple anthropometric measurements.
Am J Clin Nutr. 1980;33:27–39.
28. Blake PG, Bargman JM, Brimble KS, et al. Clinical Practice Guidelines
and Recommendations on Peritoneal Dialysis Adequacy 2011. Perit Dial
Int. 2011;31:218–239.
29. Twardowski ZJ, Nolph DK, Khanna R, et al. Peritoneal equilibration test.
Perit Dial Bull. 1987;7:138–147.
30. Mujais S, Nolph K, Gokal R, et al. Evaluation and management of
ultrafiltration problems in peritoneal dialysis. International Society for
Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in
Peritoneal Dialysis. Perit Dial Int. 2000;20(suppl 4):S5–S21.
31. Smit W, Struijk DG, Ho-Dac-Pannekeet MM, et al. Quantification of free
water transport in peritoneal dialysis. Kidney Int. 2004;66:849–854.
32. La Milia V, Di Filippo S, Crepaldi M, et al. Mini-peritoneal equilibration
test: a simple and fast method to assess free water and small solute
transport across the peritoneal membrane. Kidney Int. 2005;68:840–846.
33. Rippe B, Venturoli D. Simulations of osmotic ultrafiltration failure in
CAPD using a serial three-pore membrane/fiber matrix model. Am J
Physiol Renal Physiol. 2007;292:F1035–F1043.
34. Parikova A, Smit W, Struijk DG, et al. Analysis of fluid transport
pathways and their determinants in peritoneal dialysis patients with
ultrafiltration failure. Kidney Int. 2006;70:1988–1994.
35. La Milia V, Limardo M, Virga G, et al. Simultaneous measurement of
peritoneal glucose and free water osmotic conductances. Kidney Int.
2007;72:643–650.
36. Davies SJ. Longitudinal relationship between solute transport and
ultrafiltration capacity in peritoneal dialysis patients. Kidney Int. 2004;66:
2437–2445.
 CHAPTER 96 Peritoneal Dialysis: Principles, Techniques, and Adequacy
37. Rottembourg J, Issad B, Gallego JL, et al. Evolution of residual renal
function in patients undergoing maintenance haemodialysis or
continuous ambulatory peritoneal dialysis. Proc Eur Dial Transplant Assoc.
1983;19:397–403.
38. Adequacy of dialysis and nutrition in continuous peritoneal dialysis:
association with clinical outcomes. Canada-USA (CANUSA) Peritoneal
Dialysis Study Group. J Am Soc Nephrol. 1996;7:198–207.
39. Paniagua R, Amato D, Vonesh E, et al. Effects of increased peritoneal
clearances on mortality rates in peritoneal dialysis: ADEMEX, a
prospective, randomized, controlled trial. J Am Soc Nephrol. 2002;13:
1307–1320.
40. Brown EA, Davies SJ, Rutherford P, et al. Survival of functionally anuric
patients on automated peritoneal dialysis: the European APD Outcome
Study. J Am Soc Nephrol. 2003;14:2948–2957.
41. Lo WK, Ho YW, Li CS, et al. Effect of Kt/V on survival and clinical
outcome in CAPD patients in a randomized prospective study. Kidney
Int. 2003;64:649–656.
42. Van Biesen W, Williams JD, Covic AC, et al. Fluid status in peritoneal
dialysis patients: the European Body Composition Monitoring
(EuroBCM) study cohort. PLoS ONE. 2011;6:e17148.
43. John B, Tan BK, Dainty S, et al. Plasma volume, albumin, and fluid status
in peritoneal dialysis patients. Clin J Am Soc Nephrol. 2010;5:1463–1470.
44. Faller B, Lameire N. Evolution of clinical parameters and peritoneal
function in a cohort of CAPD patients followed over 7 years. Nephrol
Dial Transplant. 1994;9:280–286.
1113
45. Davies S, Carlsson O, Simonsen O, et al. The effects of low-sodium
peritoneal dialysis fluids on blood pressure, thirst and volume status.
Nephrol Dial Transplant. 2009;24:1609–1617.
46. Davies SJ, Woodrow G, Donovan K, et al. Icodextrin improves the fluid
status of peritoneal dialysis patients: results of a double-blind
randomized controlled trial. J Am Soc Nephrol. 2003;14:2338–2344.
47. Fortes PC, de Moraes TP, Mendes JG, et al. Insulin resistance and glucose
homeostasis in peritoneal dialysis. Perit Dial Int. 2009;29(suppl 2):
S145–S148.
48. Stenvinkel P, Heimburger O, Paultre F, et al. Strong association between
malnutrition, inflammation, and atherosclerosis in chronic renal failure.
Kidney Int. 1999;55:1899–1911.
49. U.S. Renal Data System. Excerpts from the USRDS. 2004 annual data
report. Am J Kidney Dis. 2005;45(suppl 1):S1–S270.
50. Vonesh EF, Snyder JJ, Foley RN, et al. The differential impact of risk
factors on mortality in hemodialysis and peritoneal dialysis. Kidney Int.
2004;66:2389–2401.
51. Carlsson O, Nielsen S, Zakaria el-R, et al. In vivo inhibition of
transcellular water channels (aquaporin-1) during acute peritoneal
dialysis in rats. Am J Physiol. 1996;271:H2254–H2262.
52. Venturoli D, Rippe B. Validation by computer simulation of two indirect
methods for quantification of free water transport in peritoneal dialysis.
Perit Dial Int. 2005;25:77–84.
 CHAPTER 96 Peritoneal Dialysis: Principles, Techniques, and Adequacy 1113.e1

SELF-ASSESSMENT
QUESTIONS
1. In peritoneal dialysis (PD), the fraction of aquaporin (AQP)
(ultrasmall pore)-mediated water flow is much higher for glucose
than for icodextrin (ICO) as osmotic agent. Why?
A. Glucose will induce more initial vasodilation and recruitment
of exchange vessel surface area than ICO.
B. The glucose molecules are smaller than the ICO molecules and
therefore are relatively “inefficient” as osmotic agents in small
pores, but relatively more efficient across AQP.
C. Glucose, but not ICO, will regularly induce increases in the number
of AQPs.
D. Glucose, but not ICO, can increase the peritoneal capillary filtra-
tion coefficient (LpS).
E. Oncotic agents such as ICO cannot pull fluid across AQP at all.
2. Which of the following PD catheters has a superior clinical outcome?
A. The Toronto Western catheter
B. The Swan neck catheter
C. The straight one-cuff (original) Tenckhoff catheter
D. The straight two-cuff (original) Tenckhoff catheter
E. None of the catheters above shows significant clinical superiority.
3. Long-term changes in peritoneal transport parameters usually involve:
A. Increases in the mass transfer of small solutes (e.g., PETcreat) and
marked increases in the peritoneal ultrafiltration (UF) coefficient
(LpS)
B. Reductions in small-solute mass transport (PETcreat) and increases
in the peritoneal UF coefficient (LpS)
C. Increases in small-solute transport (PETcreat) combined with no
or only moderate increases in the UF coefficient (LpS)
D. Increases in large-solute transport together with increases in UF
coefficient (LpS)
E. Increases in large-solute transport combined with reductions in
the UF coefficient (LpS)
4. Glucose-based dialysis fluids for PD, low in glucose degradation
products, have the following advantages:
A. They prevent peritoneal fibrosis and encapsulating peritoneal
sclerosis.
B. They preserve residual renal function.
C. They prevent increases in small-solute transport over treatment
time.
D. They produce higher concentrations of the dialysate effluent
marker CA-125.
E. They increase peritoneal UF capacity.
5. Which of the following is true about icodextrin as a high molecular
weight osmotic agent?
A. Icodextrin is monodispersed.
B. Icodextrin is polydispersed, but with 100% of the molecules
being larger than 3 kDa.
C. Icodextrin is polydispersed, but with 80% of the molecules being
larger than 3 kDa.
D. Icodextrin is polydispersed, but with 50% of the molecules being
larger than 3 kDa.
E. Icodextrin is polydispersed, but with 30% of the molecules being
larger than 3 kDa.
6. Net fluid reabsorption from the peritoneal cavity occurs via lymphatic
reabsorption plus backfiltration through:
A. Small pores
B. Aquaporin-1
C. Large pores
D. Larges pores + aquaporin-1
E. Small pores + large pores
 97
Complications of Peritoneal Dialysis
Simon J. Davies, Martin E. Wilkie
CATHETER MALFUNCTION
Optimal Timing and Placement of the Peritoneal
Dialysis Catheter
Catheter dysfunction adversely affects patient outcome by preventing
commencement of the chosen dialysis modality, as well as by being
disruptive to training schedules and increasing health care costs. Pub-
lished literature does not give a strong indication that one insertion
technique is better than another, although a recent meta-analysis sug-
gested an advantage of the laparoscopic compared with the open surgical
insertion technique.1 It is clear that the enthusiasm and experience of
the operator are key determinants of catheter outcome,2 and international
guidelines describe the optimal conditions for catheter insertion.3 Timing
is also important; patients randomized to the late start arm of the
Initiating Dialysis Early and Late (IDEAL) study (estimated glomerular
filtration rate [eGFR] 5 to 7 ml/min), were less likely to start on PD
than those starting early (eGFR 10 to 14 ml/min), despite PD being
their preferred treatment.4 Early catheter problems are more difficult
to manage in the absence of residual kidney function. For optimized
catheter function it is necessary that each center audit its success with
catheter placement against internationally agreed-on standards as part
of local quality improvement.2,3
Catheter Function: Inflow
A 2-liter bag of dialysate should normally take 15 minutes or less to
run into the peritoneal cavity. If inflow has stopped or significantly
slowed, mechanical causes should be suspected. After checking to ensure
that the tubing and catheter are not kinked, that all clamps or rollers
are open to the inflow position, and that any frangible seal is fully
broken, the catheter should be flushed vigorously with 20 ml of hepa-
rinized saline. If the catheter is cleared, heparin should be added (500 U/l)
to the next few cycles because the cause of the blockage is often a fibrin
plug. Should the catheter remain blocked, a plain abdominal radiograph
is required. If this shows that the catheter is in a satisfactory position
in the pelvis, an attempt to restore patency should be made with a
thrombolytic agent (urokinase, 5000 U or tissue plasminogen activator
[tPA], 2 mg in 40 ml of normal saline),5 which can be instilled into the
PD catheter for approximately 1 hour before being withdrawn. If inflow
is restored, heparin should be added to the dialysate for the next few
cycles. We no longer recommend the use of an endoscopic brush because
of safety concerns.
If the radiograph shows the catheter to be malpositioned, an attempt
should be made to reposition the catheter tip into the pelvis (Fig. 97.1).
This can be done under radiologic guidance with a sterile guidewire
inserted into the catheter, alternatively the catheter can be repositioned
at laparotomy or with the laparoscope. Sometimes the catheter becomes
wrapped in omentum, suggested usually by complete inflow and outflow
failure. This requires a partial omentectomy or an omental hitch, a
1114
surgical procedure in which the omentum is temporarily held away
from the catheter by a dissolvable suture (omentopexy). The value of
laparoscopy in this context is that it can provide a diagnosis as to the
cause of catheter flow failure and provide a solution—for example, by
repositioning the catheter, removing an omental wrap, or performing
a limited omentectomy.
Catheter Function: Outflow
The most common reason for outflow failure is constipation, although
causes of inflow failure discussed previously also should be considered.
Loading of the bowel with fecal material is often obvious on a plain
radiograph, but treatment for constipation should be initiated without
recourse to this investigation because it is so common. Constipation
should be treated with oral laxatives or an enema. Subsequently, bowel
action should be kept regular by increasing the fiber in the diet and, if
necessary, adding a mild laxative. Slow outflow can be a problem in
patients using automated peritoneal dialysis (APD), resulting in exces-
sive machine alarms. This can be managed by switching to tidal APD
and using a relatively large residual volume, for example, 25% to 50%
of the fill volume. Recently concerns have been raised about the risk
for excessive intraperitoneal dialysate volume that might occur during
tidal PD, and, as a precaution, cycler algorithms have been altered to
incorporate a complete drain into the treatment schedule.
Fibrin in the Dialysate
The mesothelial cells of the peritoneal membrane have a range of physi-
ologic functions, including the production of fibrinolytic agents such
as tPA. This process is disrupted during peritonitis when the appearance
of fibrin in the dialysate is common. If fibrin causes restriction of
dialysate flow, heparin (500 U/l) should be added to each bag. A small
number of patients have fibrin formation in the absence of peritonitis.
Immediately on drainage the bag may appear cloudy, but on standing
the fibrin will aggregate and the fluid becomes clear. The first time this
happens, a sample must be sent to the microbiology laboratory to exclude
infection. If the results of this testing prove negative, the patient can
be reassured.
FLUID LEAKS
Fluid leaks occur in which dialysate leaks out of the peritoneal cavity—
which can be either visible externally or not. It is recommended that
after PD catheter surgery, patients be allowed to heal sufficiently before
use (2 weeks) to minimize this risk. If the catheter must be used early,
low volumes should be used (start with 1 liter) in the supine position
(e.g., APD with a dry day), with the patient instructed not to mobilize
while dialysate is in the peritoneal cavity during the first 2 weeks after
catheter insertion. Although PD catheters can be used successfully as
the primary approach to manage late-presenting patients or for acute
 CHAPTER 97 Complications of Peritoneal Dialysis 1115

kidney injury, the incidence of leaks is higher under these conditions

unless precautions are taken.6,7
External Leaks
On occasion, fluid may leak from the exit site or even the incision used
to insert the catheter into the peritoneal cavity. A leak of dialysate,
which is confirmed by measuring glucose concentration in the leaking
fluid, is a risk factor for infection. It is important that PD catheters be
adequately immobilized if used for early-start PD to reduce the risk
for tugging and leak.
Curled
Connector catheter
tip
Fig. 97.1 Catheter malposition. Plain radiograph of the abdomen
with curled catheter (arrows) misplaced in the upper left abdomen.
Internal Leaks
Isolated edema of the abdominal wall suggests an internal leak from
the peritoneal cavity, either spontaneously or in association with a sur-
gical hernia. In contrast, genital edema suggests an inguinal hernia or
patent processus vaginalis. On occasion, both can be present. The site
of the leak can be visualized on computed tomography (CT) scanning
after intraperitoneal instillation of contrast material or on magnetic
resonance imaging without the use of contrast. It may be necessary for
the patient to stand or perform other maneuvers to increase intra-
abdominal pressure before the leak is demonstrated (Fig. 97.2A). An
alternative diagnostic test is to perform scintigraphy after injection of
a compound such as technetium Tc-99m–labeled diethylenetriamine-
pentaacetic acid (99mTc-DTPA; see Fig. 97.2B). A surgical repair will be
required if a major leak is visualized and should always be considered
when there is a hernia. Most leaks, however, will heal after resting or
with APD, using dry days, or temporary HD.
Hydrothorax
A pleural effusion can occur with generalized fluid overload or local
lung disease, but it is occasionally caused by a leakage of dialysate
through the diaphragm (Fig. 97.3A). This occurs more commonly on
the right side. A leak is most simply indicated by aspirating a sample
of the effusion and demonstrating that its glucose concentration is
higher than the patient’s blood glucose concentration, which can be
confirmed by scintigraphy after intraperitoneal instillation of isotope,
usually 99mTc-DTPA (see Fig. 97.3B). If one can be confident that the
pleural effusion is not caused by the PD, then PD can be continued
while the effusion is investigated and managed. Although there are

R L

A B
Fig. 97.2 Inguinal hernia during peritoneal dialysis. (A) CT scan after intraperitoneal injection of contrast
material in a male patient showing dialysate flowing into a right inguinal hernia. (A from reference 43.)
(B) Peritoneal scintigram of a male patient on peritoneal dialysis showing bilateral inguinal hernias. The left
hernia extends into the scrotum; the right hernia is less extensive.
1116 SECTION XVIII Dialytic Therapies
A B
Fig. 97.3 Hydrothorax in peritoneal dialysis. (A) Chest radiograph showing a right-sided pleural effusion
with partial collapse of the right lung caused by a diaphragmatic leak. (B) Scintigram in a peritoneal dialysis
patient showing isotope in the right hemithorax (arrows) confirming a right pleural effusion.
reports that repairing pleural leaks allows subsequent PD, the best advice
is to transfer the patient to HD unless there are very strong reasons not
to do so.
PAIN RELATED TO PERITONEAL DIALYSIS
Inflow Pain
Soon after starting PD, patients may experience pain during fluid inflow,
and occasionally pain affects the shoulders and is pleuritic, possibly
because of diaphragmatic irritation, which usually resolves over the
following days. Slowing the rate of fluid inflow will often reduce the
symptoms, and peritonitis should be excluded and treated. A small
number of individuals have persistent inflow pain, and the use of
bicarbonate-lactate–buffered dialysate at physiologic pH improves
symptoms in such patients.8
Outflow Pain
Some patients have discomfort or pain when the fluid is drained out,
which can be experienced in the genital area or rectum and is commonly
a result of pelvic irritation related to the catheter tip. This emptying
sensation is abolished when the next cycle runs in and is best treated
by leaving a small residual volume of fluid in the peritoneal cavity at
the end of the drain, for example, by using tidal APD. Tidal APD is
where a residual volume is left in the peritoneal cavity at the end of
each dialysis cycle (e.g., 20% of the drain volume). To reduce the risk
for intraperitoneal volume overload the treatment algorithm includes
at least one complete drain during and at the end of treatment.
Blood-Stained Dialysate
Blood-stained dialysate is uncommon. It is rarely serious but causes
considerable alarm to the patient. There is sometimes a clear history
of trauma to the abdomen or of unexpected strain. A range of rare
conditions are associated with this complication9; a few female patients
relate the episode to their time of ovulation or menstruation. The treat-
ment is to flush the abdomen with a few cycles of dialysate containing
heparin (500 U/l) to minimize the chances of clotting in the catheter.
The problem usually resolves spontaneously and often is visible only
in one outflow. It is unusual for the blood-stained dialysate to be associ-
ated with infection, although it is wise to have the fluid cultured. Routine
use of antibiotics is not necessary.
BOX 97.1 Relevant International Society
for Peritoneal Dialysis Guidelines
Cardiovascular and Metabolic
} ISPD Cardiovascular and Metabolic Guidelines in Adult Peritoneal Dialysis
Patients
} Part I: Assessment and Management of Various Cardiovascular Risk
Factors
} Part II: Management of Various Cardiovascular Complications
} Encapsulating Peritoneal Sclerosis
} Length of Time on Peritoneal Dialysis and Encapsulating Peritoneal Scle-
rosis: Position Paper For ISPD
Infections
} ISPD Catheter-Related Infections Recommendations: 2017 Update
} ISPD Peritonitis Recommendations: 2016 Update on Prevention and Treat-
ment 2016
} ISPD Position Statement on Reducing the Risks of Peritoneal Dialysis–Related
Infections 2011
} Peritoneal Dialysis-Related Infections Recommendations: 2010 Update
ISPD, International Society for Peritoneal Dialysis.
All available at ISPD.org
INFECTIOUS COMPLICATIONS
Peritonitis
There are wide variations in peritonitis rates both between and within
countries. Reducing peritonitis rates requires a multifaceted, multidis-
ciplinary approach based on the use of preventive measures around the
time of catheter insertion, the use of modern disconnect systems, exit
site management, and education of patients and health care profes-
sionals.10 This should be supported by regular local audit of peritoni-
tis rates including causative organisms and local sensitivities, which is
increasingly important because of the emergence of resistant organ-
isms, and the requirement to use antibiotics effectively. Root cause
analysis (e.g., inquiring about breaches in sterile technique) should
be performed after each episode of PD peritonitis, with retraining
as appropriate. Guidelines for the diagnosis and management of PD
 CHAPTER 97
peritonitis are published by the International Society for Peritoneal
Dialysis (ISPD; www.ispd.org) (Box 97.1).10 The spectrum of perito-
nitis and its management in children have also recently been described
in detail.11 The reader is directed to a detailed review on reducing
peritonitis risk.12
Diagnosis of Peritonitis
Peritonitis should be suspected in any patient who develops abdominal
pain or a cloudy bag when PD fluid is drained; patients with these
symptoms should be advised to contact their dialysis center immediately.
Fever may be present but is not a universal feature. Samples of the
dialysate should be taken for cell count and microbiologic examination.
The diagnosis is confirmed by finding more than 100 white blood cells/
mm3 (1 × 107 cells/l). A Gram stain of the spun deposit should be
performed to help identify the type of causative organism, although
initial treatment will usually be empiric pending culture and sensitivity
results. Various culture techniques have been proposed, but white cell
lysis and inoculation into blood culture media is often helpful in increas-
ing the yield of a positive growth.
The dialysate leukocyte count will be affected by dwell length, and
this needs to be considered in APD patients. In short dwells, the count
will be lower, and under these circumstances, if the proportion of cells
that are neutrophils exceeds 50%, empiric treatment of peritonitis should
be commenced. Conversely, if the patient has had a dry abdomen during
the day, the initial drain on connection may be cloudy. This will clear
within one or two cycles, and most of the cells found will be mono-
nuclear leukocytes.
Treatment of Peritonitis
The empiric treatment of peritonitis will vary according to center and
should be developed in close collaboration with the local microbiology
service, taking into account sensitivity patterns and infection control
policy. Initial regimens must cover both gram-positive and gram-negative
organisms; the latest ISPD guidelines (www.ispd.org) give examples of
appropriate antibiotics and their doses, including vancomycin, cepha-
losporins, and aminoglycosides. Antibiotic regimens are adjusted as
soon as culture results are available, usually after about 48 hours.10 The
preferred route of administration is intraperitoneal (IP) unless the
patient has features of systemic sepsis. IP gentamicin can be administered
as daily intermittent dosing at a dose of 0.6 mg/kg/day (aiming to main-
tain the trough serum concentration of <2 mg/l); IP vancomycin also
can be administered intermittently every 5 to 7 days, at a dose of 15 to
30 mg/kg, aiming to maintain the serum vancomycin level above 15 μg/
ml. IP cephalosporin be administered either continuously (in each
exchange) or on a daily intermittent basis.10
Dosage regimens will depend on whether the patient is on CAPD
or APD. For CAPD, the antibiotic is administered as a loading dose in
the first bag and then as a maintenance dose in subsequent bags. The
intermittent IP dose can be given in the day dwell of APD patients;
however, APD results in a higher peritoneal clearance of antibiotics
than CAPD, and therefore extrapolation of data from CAPD to APD
may result in underdosing.
Once the culture result is available, the regimen should be modified
accordingly (Table 97.1). If the organism is methicillin-resistant Staphy-
lococcus aureus (MRSA), vancomycin will be continued as part of the
regimen. If the culture is negative, empiric therapy should be continued
for 2 weeks, assuming there is a clinical response. If a gram-negative
organism is identified, the subsequent management will depend on the
sensitivity (Fig. 97.4). The isolation of multiple organisms with or
without anaerobes strongly suggests perforation of the small or large
intestine or biliary system. Metronidazole should be added to the regimen
to cover anaerobic organisms, antibiotic therapy augmented to
Complications of Peritoneal Dialysis 1117
TABLE 97.1 Antibiotic Regimens for
Bacterial Peritoneal Dialysis Peritonitis
Culture Antibiotic
Gram positive: Based on Vancomycin or other appropriate antibiotic
sensitivities
Coagulase-negative Treat for 14 days
staphylococci
Staphylococcus aureus* Treat for 21 days: Screen for carriage
Enterococci Treat for 21 days
Other streptococci Treat for 14 days
Gram-negative bacilli or mixed Continue gram-negative coverage based
bacterial growth on sensitivities Consider switching to
third- or fourth-generation cephalosporins
Pseudomonas* or Two antibiotics based on sensitivity, treat
Stenotrophomonas spp. for 21-28 days
Other gram-negative bacilli Treat for 21 days
Mixed gram-negative or gram negative +
gram-positive, consider metronidazole
and ampicillin/vancomycin.
From reference 10.
*Examine for exit site or catheter tunnel infection.
Suggested antibiotic regimens when dialysate fluid culture is
available. Except for culture-negative episodes, empiric treatment is
stopped once the sensitivities are known. All antibiotic regimens
should be adjusted for local microbiologic practices.
intravenous administration, and prompt surgical review obtained with
necessary imaging (CT scan if appropriate).
A wide variety of antibiotics other than those cited have been used
with success, and these are documented in the ISPD 2016 guideline.10
A commonly used strategy is to include an oral quinolone, such as
ciprofloxacin. There is debate surrounding the role of aminoglycosides—
advantages being simplicity of use and good coverage for gram-negative
organisms; however, there are concerns regarding ototoxicity and neph-
rotoxicity, the former of which is irreversible. Reports regarding the
impact of these agents on residual renal function are inconsistent, but
serious episodes of peritonitis tend to adversely affect residual renal
function. It is, however, advisable to avoid recurrent or protracted courses
of aminoglycosides, with an early switch to alternative agents (e.g.,
third-generation cephalosporins) if they are used as empiric first-line
treatment. There is evidence for the use of concomitant N-acetylcysteine,
which should be considered to block the ototoxicity.13 Current recom-
mendations are that for gram-positive organisms, therapy should be
for 14 days except in the case of S. aureus, for which 21 days is suggested.
For culture-negative episodes, 14 days of therapy should suffice. The
same is true in the case of single-organism gram-negative peritonitis.
Many patients can be treated successfully as outpatients. It is extremely
important, however, that they be followed either in the clinic or by
telephone. In most patients, clinical resolution (as judged by the clearing
of the bags) starts within 48 hours. If there is no improvement within
96 hours despite use of the correct antibiotic, as judged by sensitivity
tests, the fluid must be retested by cell count, Gram stain, and culture.
The ISPD recommends that the catheter be removed if there is no
improvement in 5 days; however, in a severe infection this should be
done earlier, and in a more indolent case the period of observation can
be longer. A specific recommendation is that the catheter should be
1118 SECTION XVIII Dialytic Therapies

Overview of the Management of Peritonitis

Clinical suspicion of peritonitis

Repeat on next
Check dialysate white blood cell count exchange if
symptoms persist

>100 cells per mm3 <100 cells per mm3

positive
Gram stain Commence empiric antibiotics*
(e.g., cefazolin, cefalothin, aminoglycoside,
negative depending on residual renal function and
negative result of Gram stain)

Refine antibiotics
Culture result (see Table 97-1) Resolution

Multiple or Despite appropriate antibiotics

anaerobic organisms symptoms worsen or persist

Catheter removal ! laparotomy

Fig. 97.4 Overview of the management of peritonitis.

removed where a Pseudomonas or S. aureus peritonitis occurs in con-
junction with an exit site or tunnel infection.10 In addition, the possibility
of intraabdominal or gynecologic disease or the presence of unusual
organisms such as mycobacteria should be considered. Under these
circumstances, a mini-laparotomy should be performed to exclude
intraabdominal disease, and if mycobacterial infection is suspected, a
peritoneal biopsy specimen should be obtained for culture.
Fungal Peritonitis
If peritonitis is caused by yeasts or fungi, the peritoneal catheter should
be removed promptly. This should be combined with treatment with
an appropriate antifungal for at least 2 weeks after catheter removal.
Fungal peritonitis is a serious complication of PD, commonly requiring
hospitalization and transfer to hemodialysis (HD), with a high associ-
ated mortality. It is essential to review the appropriate antifungal agent
with the local microbiologic team; options are described in some detail
in the 2016 peritonitis update from the ISPD.10 Amphotericin B should
not be given intraperitoneally because it causes chemical peritonitis
and pain. Appropriate antifungal therapy should be continued for at
least 2 weeks after catheter removal.
Relapsing Peritonitis
Relapsing peritonitis is defined as infection caused by the same organism
as the original infection occurring within 4 weeks, whereas recurrent
peritonitis is defined as a different organism within 4 weeks of comple-
tion of an appropriate course of antibiotics. In general, the advice is to
treat as for a primary infection but to try to establish an underlying
cause. For example, recurrence of S. aureus infection should trigger a
search for pericatheter infection. If enterococci or gram-negative organ-
isms are the cause of a relapse, the possibility of intraabdominal disease
or an abscess should be considered (although these organisms are fre-
quently water-borne). If a patient has other gastrointestinal symptoms,
such as change in bowel habit, appropriate investigation should be
conducted. Some organisms (including coagulase-negative staphylococci)
produce biofilm that can lead to a relapse of the infection. Consideration
should be given to changing the PD catheter once the infection has
been treated; of course, the catheter will need to be removed if the
infection does not respond to treatment. Current practice in most units
is to allow up to 3 weeks of treatment before a new catheter is inserted.
Culture-Negative Peritonitis
Culture-negative peritonitis is associated with increased risk for treatment
failure. Commonly the cause relates to the sampling technique or the
microbiologic approach; alternatively, concurrent antibiotic use may be
responsible. It is important to be aware of the possibility of fastidious
organisms (e.g., atypical mycobacteria, suspicious of contaminated water
sources, or yeasts). In addition, other causes of peritoneal inflamma-
tion may responsible; these include the presence of an intraabdominal
malignancy or surgical pathology or eosinophilic reactions—for example,
in the case of vancomycin allergy or some fungal infections. Chylous
effluent is a rare finding in PD; the cause is often unclear, but if recur-
rent, conditions affecting lymphatic drainage should be considered.
Exit Site Infection
Exit site infection (ESI) is an important complication of long-term PD.
The diagnosis is suspected on clinical grounds, usually by the presence
 CHAPTER 97
Fig. 97.5 Exit site infection. A severe exit site infection that has
exposed the outer cuff of the catheter.
of marked erythema or discharge from the exit site (Fig. 97.5). A scoring
system for exit sites has been developed to determine the likelihood
of infection and grade its severity, with points assigned for crusting,
swelling, pain, and discharge according to severity; if the discharge is
purulent, this mandates treatment.14 Extension of the infection into
the tunnel may be assessed either clinically or by ultrasound. The most
common infecting organism is S. aureus. There is evidence for the
use of prophylactic topical antibiotics at the exit site, the strongest
being for mupirocin for the prevention of ESI caused by S. aureus.14
There is also evidence for the use of topical gentamicin, although there
were some reports of an increase in ESI caused by Enterobacteria-
ceae, Pseudomonas spp., and probably nontuberculous mycobacteria
after a change of prophylactic protocol from topical mupirocin to
gentamicin.10
All suspected infected exit sites should be swabbed; routine swab-
bing of healthy exit sites should be avoided, and incidental bacterial
growth does not require treatment. Unless there is prior evidence that
the patient carries MRSA or Pseudomonas, initial treatment should be
with an antibiotic effective against S. aureus—such as a penicillinase
resistant penicillin (e.g., dicloxacillin or flucloxacillin—it is important
to be aware of the risk for associated hepatotoxicity with the latter) or
a first-generation cephalosporin if the patient is allergic to penicillin.
In most patients, the drug can be given orally; but if the individual
is systemically ill, the antibiotics should be administered intrave-
nously until clinical improvement occurs. Hospitalization, parenteral
antibiotics, and often urgent catheter removal are required if there
is evidence of spread into the tunnel. If the infection is with MRSA,
eradication therapy should be attempted with systemic vancomycin,
as for peritonitis. Should the culture grow a gram-negative organism,
ciprofloxacin (500 mg twice daily orally) will be effective empiric treat-
ment in most patients. ESIs caused by Pseudomonas spp. are particu-
larly difficult to treat and often require prolonged therapy with two
antibiotics.
Treatment is recommended for a minimum of 2 weeks, extended
to 3 weeks in Pseudomonas infections. In gram-positive infections, if
there is no improvement within 7 days, ultrasound of the catheter
tunnel should be performed because a collection of fluid around the
catheter signifies a tunnel infection. If complete healing does not take
place after 4 weeks of therapy, further measures should be considered,
such as exteriorizing and shaving the outer cuff because it may be
involved in the infection. If the infection persists or relapses, catheter
removal must be considered because there is a high risk that the ESI
will lead to peritonitis. It is important that the new exit site be formed
in a different part of the anterior abdominal wall.
Complications of Peritoneal Dialysis 1119
REDUCED ULTRAFILTRATION AND
ULTRAFILTRATION FAILURE
Definition and Significance of Ultrafiltration Failure
There are two complementary approaches to defining ultrafiltration
(UF) failure. The first is based solely on the net fluid removal (termed
ultrafiltration capacity) from a standard 4-hour peritoneal equilibration
test (PET). The conduct and interpretation of the PET are further dis-
cussed in Chapter 97. Account should be taken of the overfill of dialysis
bags by the manufacturers, which can be as much as 200 ml. A net UF
capacity below 400 ml with a hypertonic glucose exchange (3.86%) is
indicative of an inadequate membrane,15 bearing in mind that this may
not be clinically relevant in a patient with well-preserved residual renal
function. If a middle-strength glucose solution is used (2.27%), the
equivalent value is 0 ml (again excluding overfill). Although this defini-
tion is clear enough, the main limitation is that it relies on a single
measurement of UF capacity, which is subject to significant error (coef-
ficient of variation is up to 25%). The second approach to defining
UF failure is more holistic in that it considers patient factors that
affect fluid status (e.g., comorbid conditions) and an acceptable glucose
exposure required to maintain adequate hydration. Many clinicians
now take the view that regular use of hypertonic solutions is not
acceptable unless the life expectancy is shorter than the likely time to
development of severe membrane failure and its complications, unusual
before 5 years.
UF failure is a significant cause of technique failure16; it results in
low UF, which in turn increases the risk for mortality in anuric patients17,18
and is also a risk factor for encapsulating peritoneal sclerosis (EPS).19
Although it is impossible to set a fluid removal goal that applies to all
patients, the European Automated Peritoneal Dialysis Outcomes Study
(EAPOS) found that anuric patients who failed to reach an UF target
of more than 750 ml/day had less efficient membranes (specifically
lower osmotic conductance, see later) and higher mortality.18 Patients
whose total fluid removal is less than 1 l/day because of poor UF should
have their membrane function assessed.
Establishing the Causes of Ultrafiltration Failure
Failure of the membrane to ultrafiltrate needs to be distinguished from
other causes of inadequate peritoneal fluid removal such as catheter
dysfunction, leak, or excessive fluid reabsorption.20 The latter can occur
if the intraperitoneal cavity pressure is too high, suspected if the UF
falls after an increase in dialysate volume. If there is doubt, a dialysate
sodium concentration below 125 mmol/l 1 hour into a PET using 3.86%
glucose, an indicator of preserved sodium sieving (see later) suggests
that UF is preserved.
There are two main causes of UF failure: a fast peritoneal solute
transport rate (fPSTR) or low membrane UF efficiency despite a pre-
served osmotic gradient, termed reduced osmotic conductance. Both can
exist at the start of PD or can be acquired with time on therapy, although
it is rare for a patient to develop reduced osmotic conductance without
also having rapid transport.
Fast Peritoneal Solute Transport Rate–Related
Ultrafiltration Failure: Diagnosis and Management
With the 4-hour PET, a dialysate–plasma creatinine ratio greater than
average (0.64) could contribute to poor UF. This is because more rapid
diffusion of small solute across the membrane leads to earlier dissipa-
tion of the osmotic gradient driving UF. Furthermore, once the gradient
is lost, membranes with a larger diffusive area will reabsorb fluid more
rapidly. In continuous ambulatory PD patients, fPSTR is associated
with increased mortality, technique failure, and hospitalization,21 whereas
this association is attenuated or possibly reversed when APD is used.22,23
1120 SECTION XVIII Dialytic Therapies
Thus both theoretically and empirically the short exchanges used in
APD prescription are associated with better outcomes in fPSTR-associated
poor UF. Prevention of fluid reabsorption during the long day or night
exchange is also required in these patients, and this can be achieved by
use of icodextrin (polyglucose solution), which also improves the fluid
status24 and reduces episodes of fluid overload.25 The main determinant
of fPSTR is increased intraperitoneal inflammation, which is indepen-
dent of systemic inflammation.26 Only the latter is an independent
predictor of mortality.
Low Osmotic Conductance–Related Ultrafiltration
Failure: Diagnosis and Management
This problem should be suspected if UF failure persists despite adjust-
ment of the prescription to accommodate the peritoneal solute transport
rate (PSTR). Osmotic conductance is a measure of the efficiency of the
peritoneal membrane to ultrafiltrate for a given osmotic agent, typically
glucose. Reduced osmotic conductance can be demonstrated quite easily
in the clinic. Sodium sieving is the consequence of free water entering
the peritoneal cavity via the transcellular endothelial aquaporin pathway,
resulting in a drop resulting from dilution in the dialysate sodium
concentration; it is independent of the sodium-coupled UF that occurs
across endothelial tight junctions. Thus the absence of a fall in the
dialysate sodium concentration 1 hour after using a high glucose exchange
indicates the lack of sodium sieving, which implies reduced free water
UF. This can be combined with the double–mini-PET,20 which requires
back-to-back 1-hour exchanges using low (1.36%) and high (3.86%)
glucose concentrations; a difference of less than 400 ml net UF between
the two exchanges indicates poor osmotic conductance. The two causes
so far identified are reduced aquaporin function, possibly constitutive
and thus present at the start of treatment, and progressive fibrosis of
the membrane as a result of acquired membrane injury. There is no
specific treatment, so clinical effort should focus on prevention (see
next section) and timely switch to HD or transplantation.
CHANGES IN PERITONEAL
STRUCTURE AND FUNCTION
It is widely assumed that alterations in peritoneal function, a combina-
tion of an increased PSTR and loss of osmotic conductance, are related
to structural changes in the peritoneal membrane.27 There is accumulat-
ing evidence that continuous exposure to dialysis solution components
and repeated episodes of bacterial peritonitis are the main drivers of
this process (Fig. 97.6). The relationship between structure and function
is becoming clearer: increased PSTR is likely to reflect a greater vascular
surface area, whereas loss of osmotic conductance requires an additional
mechanism that is associated with progressive membrane fibrosis and
an increased risk for EPS. The submesothelial collagenous zone shows
progressive increase in thickness with time on PD (Figs. 97.7 and 97.8),
and this is associated with progressive changes to the structure of small
venules ranging from subtle thickening of the subendothelial matrix
to complete obliteration of vessels (Fig. 97.9).28,29 This process is accom-
panied by a reduction in sodium sieving, implying reduced free water
transport, but no change in aquaporin expression, suggesting that the
fibrosis is the main cause of UF failure.30
Preventing Membrane Injury
The main clinical factors associated with more rapid and severe mem-
brane injury are early loss of residual renal function, recurrent or severe
peritonitis, and the earlier use of higher glucose–containing solutions
(often associated with loss of diuresis but an independent risk factor).31
Hypertonic solutions may induce injury because of direct glucose toxic-
ity; glucose degradation products (GDPs) manifest as a result of the
M
M
Fig. 97.6 Peritonitis. Scanning electron micrograph of the peritoneum
from a patient receiving peritoneal dialysis who has peritonitis. The small
round cells (arrows) are phagocytes, which are widely distributed among
the mesothelial cells (M). (Magnification, ×1800.)
sterilization process, or both. The prevention of membrane injury should
focus on all of these drivers and include (1) preservation of residual
renal function by avoiding both volume depletion and the use of
angiotensin-converting enzyme (ACE) inhibitors and angiotensin recep-
tor blockers (ARBs); (2) use of loop diuretics to maintain urine volume
and delay use of hypertonic exchanges; (3) use of icodextrin in the long
exchange; (4) avoidance of peritonitis; and (5) use of low-GDP neutral
pH solutions.32 The balANZ study shows that the increase in PSTR
over the first 2 years of PD is prevented by use of ultralow-GDP dialysis
fluid. More importantly, this study showed that achievement of less UF,
lower use of hypertonic glucose, and in particular low-GDP solutions
early in the course of PD, now confirmed in meta-analyses of several
trials is associated with preservation of residual kidney function.25,33
This, combined with trial evidence that fluid status is stable in patients
with residual kidney function,34 supports the main strategy clinicians
should adopt in preserving the membrane—prescribing to maintain
adequate but not excessive UF, which will only drive thirst and increase
the risk for volume depletion.
Encapsulating Peritoneal Sclerosis
A minority of patients on PD develop EPS, in which the bowel is envel-
oped in a thick cocoon of fibrous tissue, causing intestinal obstruction
(Fig. 97.10).19 It is variable in severity but may be life-threatening, causing
death from malnutrition or intraabdominal catastrophe; but with expe-
rienced management by a multidisciplinary team, overall survival com-
pares well with that of matched controls. Diagnosis of this syndrome
requires both clinical signs and symptoms of bowel obstruction leading
to weight loss and malnutrition (with or without features of systemic
inflammation) combined with either typical features on imaging (CT
scanning) or confirmation of fibrous cocooning at laparotomy. Although
UF failure is a risk factor for EPS (especially when there is also loss of
osmotic conductance), EPS appears to be a different pathologic process
that predominantly affects the visceral membrane, is usually associated
with another trigger (such as severe peritonitis or interruption of PD),
and frequently has a systemic inflammatory phase (biopsy material
more often shows inflammation and fibrinous exudates).
The single most important risk factor for EPS is time on PD; at 5
years the incidence is 2% to 3%, whereas by 10 years, this rises to
6% to 20%.19 Recent reports from Japan35 and the Netherlands suggest
that the incidence of EPS is decreasing, possibly because of a better
 CHAPTER 97 Complications of Peritoneal Dialysis 1121

Peritoneal Membrane Thickening in Peritoneal Dialysis

2000
Normal vs all P = .00001
Membrane thickness (mm) HD vs PD P = .0049

PD P = .0049

1000

0
Normal Undialyzed HD 0-24 25-48 49-72 73-96 97+
CKD months months months months months
PD
Fig. 97.7 Peritoneal membrane thickening in peritoneal dialysis (PD). The thickness of the subme-
sothelial collagenous zone of the peritoneal membrane in normal individuals, in undialyzed patients with
advanced chronic kidney disease (CKD), patients with uremia, in patients receiving hemodialysis (HD), and
in those who have received PD for different periods. Membrane thickness is significantly increased in all
uremic and dialysis patients compared with normal individuals. Membrane thickness increases significantly
with duration of PD and is increased in PD patients as a group compared with HD patients.

A 100µm
B 100µm

Fig. 97.8 Morphologic changes in the parietal peritoneal membrane. (A) Normal. (B) A patient who
has been on peritoneal dialysis (PD) for 10 years. Note the marked thickening of the submesothelial compact
zone (arrows). (Toluidine blue stain.)

understanding of the management of risk factors. There is increasing
evidence that surgical treatment (extensive adhesion lysis and excision
of the peritoneum while avoiding enterotomy) is most effective, espe-
cially when there are obstructive symptoms. This should be undertaken
by an experienced surgical team, which can achieve cure rates of 70%
to 80%. Parenteral nutrition can be used as a preparation for surgery
and occasionally as a long-term solution. In about 50% of patients,
symptoms are less severe and gradually resolve. There is no role for
preemptive screening by CT scanning, but this is helpful in diagnosis.
Most commonly, EPS develops after transfer from PD to either HD or
transplantation; but if it develops in a patient on PD, the consensus is
that PD should be stopped to avoid continued exposure to nonphysi-
ologic dialysis solutions. Other strategies, such as continued irrigation,
dual-modality treatment with PD and HD, and use of antifibrotic drugs
such as tamoxifen, are practiced, but an evidence base for such manage-
ment is lacking.
NUTRITIONAL AND METABOLIC COMPLICATIONS
Undernutrition
Cross-sectional surveys of patients receiving PD show that about 40%
have evidence of mild and 8% severe protein-calorie depletion as judged
1122 SECTION XVIII Dialytic Therapies
A B
10µm
Fig. 97.9 Blood vessels in the parietal peritoneum: transverse sections of peritoneal arterioles.
(A) Normal. (B) Vasculopathy in a patient on peritoneal dialysis; the vascular lumen (arrows) is occluded by
connective tissue containing fine calcific stippling.
Fig. 97.10 Encapsulating peritoneal sclerosis. Abdominal CT scan
from a patient with encapsulating peritoneal sclerosis. Red arrows indi-
cate thickened parietal peritoneum with calcification; green arrows indicate
thickened visceral peritoneum forming a cocoon containing loops of
bowel.
by the subjective global assessment of nutritional state. Malnutrition is
a risk factor for morbidity and mortality of patients on PD and often
associated with systemic inflammation. The assessment and management
of malnutrition are discussed further in Chapter 86. One obvious con-
tributing factor is protein loss through the peritoneum, which averages
8 g/day. Protein loss is proportional to effective membrane area and so
is most marked during peritonitis and in patients with fast peritoneal
transport. The ensuing hypoalbuminemia exacerbates the extravascular
extracellular fluid expansion in these patients.36 Therefore it has been
recommended that PD patients should consume daily at least 1.2 to 1.3 g
of protein per kilogram of body weight. In practice, many patients take
only about 0.8 g/kg/day, and nitrogen balance is maintained partly as a
result of calories from dialysate. However, especially once patients are
anuric, there is a progressive loss in lean body mass.34 Despite concerns
10µm
over hypoalbuminemia in peritoneal dialysis patients, the association
with mortality is not worse than for HD patients.37
PD patients have abnormal eating behavior with smaller meals, slow
eating, and impaired gastric emptying, which causes nausea, especially
in patients with diabetes. This is worst when using more hypertonic
glucose and least severe with icodextrin. Amino acid–based dialysate
improves nitrogen balance in malnourished patients, but the long-term
nutritional benefit is marginal.38
Acid-Base Status
Correction of acidosis is best achieved by use of dialysate with higher
levels of potential buffer,39 but if necessary, oral bicarbonate may be
added. There is evidence that correction of acidosis, by whatever means,
to within the upper half of the normal range for serum bicarbon-
ate reduces protein catabolism, resulting in weight gain and increased
midarm muscle circumference.38 The use of amino acid–containing
dialysate fluid can worsen acid-base status, requiring close monitoring.
Lipids and Obesity
PD results in significant daily glucose absorption, which may range
from 80 to 200 g/day (300 to 800 kcal). Therefore PD patients tend to
develop features of metabolic syndrome: central obesity, hyperglycemia,
dyslipidemia, and hyperinsulinemia; they may even develop frank dia-
betes, although there is no evidence that this or worsening obesity is
more common than in HD patients.40 These problems can be reduced
by use of icodextrin and amino acid solutions in place of glucose with
better glycemic control in diabetics.41 Blood glucose monitoring in
diabetic patients using icodextrin must not use glucose dehydrogenase
pyrroloquinoline quinone (GDH-PQQ) test strips because this will
lead to falsely high estimates and risk for severe hypoglycemia.
Despite these concerns, there is no evidence to suggest that PD
should be avoided in obese patients even though the survival advantage
seen in HD associated with a higher body mass index is not seen
with PD.42
REFERENCES
1. Hagen SM, Lafranca JA, Steyerberg EW, et al. Laparoscopic versus open
peritoneal dialysis catheter insertion: a meta-analysis. Mandell MS, ed.
PLoS ONE. 2013;8:e56351.
 CHAPTER 97
2. Goh BL, Ganeshadeva Yudisthra M, Lim TO. Establishing learning curve
for Tenckhoff catheter insertion by interventional nephrologist using
CUSUM analysis: How many procedures and in which situation? Semin
Dial. 2009;22:199–203.
3. Figueiredo A, Goh B, Jenkins S, et al. Clinical practice guidelines for
peritoneal access. Perit Dial Int. 2010;30:424–429.
4. Johnson DW, Wong MG, Cooper BA, et al. Effect of timing of dialysis
commencement on clinical outcomes of patients with planned initiation
of peritoneal dialysis in the ideal trial. Perit Dial Int. 2012;32:595–604.
5. Shea M, Hmiel SP, Beck AM. Use of tissue plasminogen activator for
thrombolysis in occluded peritoneal dialysis catheters in children. Adv
Perit Dial. 2001;17:249–252.
6. Povlsen J V, Ivarsen P. How to start the late referred ESRD patient
urgently on chronic APD. Nephrol Dial Transplant. 2006;21 Suppl 2:
ii56–ii59.
7. Cullis B, Abdelraheem M, Abrahams G, et al. Peritoneal dialysis for acute
kidney injury. Perit Dial Int. 2014;34:494–517.
8. Mactier RA, Sprosen TS, Gokal R, et al. Bicarbonate and bicarbonate/
lactate peritoneal dialysis solutions for the treatment of infusion pain.
Kidney Int. 1998;53:1061–1067.
9. Lew SQ. Hemoperitoneum: bloody peritoneal dialysate in ESRD patients
receiving peritoneal dialysis. Perit Dial Int. 2007;27:226–233.
10. Li PK-T, Szeto CC, Piraino B, et al. ISPD Peritonitis Recommendations:
2016 Update on Prevention and Treatment. Perit Dial Int. 2016;36:
481–508.
11. Warady BA, Bakkaloglu S, Newland J, et al. Consensus guidelines for the
prevention and treatment of catheter-related infections and peritonitis in
pediatric patients receiving peritoneal dialysis: 2012 update. Perit Dial Int.
2012;32:S32–S86.
12. Campbell DJ, Johnson DW, Mudge DW, et al. Prevention of peritoneal
dialysis-related infections. Nephrol Dial Transplant. 2015;30:1461–1472.
13. Tokgoz B, Ucar C, Kocyigit I, et al. Protective effect of N-acetylcysteine
from drug-induced ototoxicity in uraemic patients with CAPD
peritonitis. Nephrol Dial Transplant. 2011;26:4073–4078.
14. Szeto CC, Li P, Johnson DW, et al. ISPD Catheter-related infections
recommendations: 2017 update. Perit Dial Int. 2017;37(2):141–154.
15. Smit W, van Dijk P, Langedijk MJ, et al. Peritoneal function and
assessment of reference values using a 3.86% glucose solution. Perit Dial
Int. 2003;23:440–449.
16. Davies SJ, Phillips L, Griffiths AM, et al. What really happens to people
on long-term peritoneal dialysis? Kidney Int. 1998;54:2207–2217.
17. Jansen MA, Termorshuizen F, Korevaar JC, et al. Predictors of survival in
anuric peritoneal dialysis patients. Kidney Int. 2005;68:1199–1205.
18. Brown EA, Davies SJ, Rutherford P, et al. Survival of functionally anuric
patients on automated peritoneal dialysis: the European APD Outcome
Study. J Am Soc Nephrol. 2003;14:2948–2957.
19. Brown EA, Bargman J, van Biesen W, et al. Length of Time on Peritoneal
Dialysis and Encapsulating Peritoneal Sclerosis - Position Paper for ISPD:
2017 Update. Perit Dial Int. 2017;37(4):362–374.
20. van Biesen W, Heimburger O, Krediet R, et al. Evaluation of peritoneal
membrane characteristics: clinical advice for prescription management by
the ERBP working group. Nephrol Dial Transplant. 2010;25:2052–2062.
21. Brimble KS, Walker M, Margetts PJ, et al. Meta-analysis: peritoneal
membrane transport, mortality, and technique failure in peritoneal
dialysis. J Am Soc Nephrol. 2006;17:2591–2598.
22. Johnson DW, Hawley CM, Mcdonald SP, et al. Superior survival of high
transporters treated with automated versus continuous ambulatory
peritoneal dialysis. Nephrol Dial Transplant. 2010;25:1973–1979.
Complications of Peritoneal Dialysis 1123
23. Mehrotra R, Ravel V, Streja E, et al. Peritoneal Equilibration Test and
Patient Outcomes. Clin J Am Soc Nephrol. 2015;10:1990–2001.
24. Davies SJ, Woodrow G, Donovan K, et al. Icodextrin improves the fluid
status of peritoneal dialysis patients: results of a double-blind
randomized controlled trial. J Am Soc Nephrol. 2003;14:2338–2344.
25. Cho Y, Johnson DW, Craig JC, et al. Biocompatible dialysis fluids for
peritoneal dialysis. Cochrane Database Syst Rev. 2014;(3):CD007554.
26. Lambie M, Chess J, Donovan KL, et al. Independent effects of systemic
and peritoneal inflammation on peritoneal dialysis survival. J Am Soc
Nephrol. 2013;24:2071–2080.
27. Davies SJ. Longitudinal relationship between solute transport and
ultrafiltration capacity in peritoneal dialysis patients. Kidney Int. 2004;66:
2437–2445.
28. Williams JD, Craig KJ, Topley N, et al. Morphologic changes in the
peritoneal membrane of patients with renal disease. J Am Soc Nephrol.
2002;13:470–479.
29. Honda K, Nitta K, Horita S, et al. Morphological changes in the
peritoneal vasculature of patients on CAPD with ultrafiltration failure.
Nephron. 1996;72:171–176.
30. Morelle J, Sow A, Hautem N, et al. Interstitial Fibrosis Restricts Osmotic
Water Transport in Encapsulating Peritoneal Sclerosis. J Am Soc Nephrol.
2015;26:2521–2533.
31. Lambie ML, John B, Mushahar L, et al. The peritoneal osmotic
conductance is low well before the diagnosis of encapsulating peritoneal
sclerosis is made. Kidney Int. 2010;78:611–618.
32. Davies SJ, Mushahar L, Yu Z, et al. Determinants of peritoneal membrane
function over time. Semin Nephrol. 2011;31:172–182.
33. Johnson DW, Brown FG, Clarke M, et al. Effects of biocompatible versus
standard fluid on peritoneal dialysis outcomes. J Am Soc Nephrol. 2012;
23:1097–1107.
34. Tan BK, Yu Z, Fang W, et al. Longitudinal bioimpedance vector plots add
little value to fluid management of peritoneal dialysis patients. Kidney
Int. 2016;89:487–497.
35. Nakayama M, Miyazaki M, Honda K, et al. Encapsulating peritoneal
sclerosis in the era of a multi-disciplinary approach based on
biocompatible solutions: the NEXT-PD study. Perit Dial Int. 2014;34:
766–774.
36. John B, Tan BK, Dainty S, et al. Plasma volume, albumin, and fluid
status in peritoneal dialysis patients. Clin J Am Soc Nephrol. 2010;5:
1463–1470.
37. Mehrotra R, Duong U, Jiwakanon S, et al. Serum albumin as a predictor
of mortality in peritoneal dialysis: comparisons with hemodialysis. Am J
Kidney Dis. 2011;58:418–428.
38. Li FK, Chan LYY, Woo JCY, et al. A 3-year, prospective, randomized,
controlled study on amino acid dialysate in patients on CAPD. Am J
Kidney Dis. 2003;42:173–183.
39. Mujais S. Acid-base profile in patients on PD. Kidney Int Suppl. 2003;
S26–S36.
40. Mehrotra R, Devuyst O, Davies SJ, et al. The Current State of Peritoneal
Dialysis. J Am Soc Nephrol. 2016;27:3238–3252.
41. Li PKT, Culleton BF, Ariza A, et al. Randomized, controlled trial of
glucose-sparing peritoneal dialysis in diabetic patients. J Am Soc Nephrol.
2013;24:1889–1900.
42. Ahmadi S-F, Zahmatkesh G, Streja E, et al. Association of body mass
index with mortality in peritoneal dialysis patients: a systematic review
and meta-analysis. Perit Dial Int. 2015;36:315–325.
43. Tintillier M, Coche E, Malaise J, et al. Peritoneal dialysis and an inguinal
hernia. Lancet. 2003;362:1893.
 CHAPTER 97 Complications of Peritoneal Dialysis 1123.e1

SELF-ASSESSMENT
QUESTIONS
1. Regarding catheter function, which of the following statements is/
are false?
A. Introducing the routine use of laparoscopic technique for catheter
insertion will improve early catheter survival more than carefully
audited standard methods used by an experienced surgeon.
B. Slow catheter drainage is most commonly a result of
constipation.
C. Pain on draining in (“inflow pain”) is best solved by use of tidal
peritoneal dialysis (PD).
D. Pain on draining out is best solved in automated PD (APD)
patients by use of tidal PD.
E. Poor drainage associated with edema in the genital area indicates
an inguinal hernia or patent processus vaginalis.
2. Regarding peritonitis and infection, which of the following state-
ments is/are false?
A. Treatment of suspected peritonitis should always commence with
antibiotics covering both gram-positive and gram-negative
organisms.
B. Fungal peritonitis usually can be successfully treated with intra-
peritoneal agents without requiring catheter removal.
C. Redness and pain at the exit site always should be treated imme-
diately with oral antibiotics.
D. Prophylactic use of mupirocin or gentamicin at the exit site has
been shown to reduce the chances of peritonitis.
E. Culture of more than one organism in a patient with peritonitis
should raise serious concerns of a perforated viscus and lead to
mini-laparotomy as well as catheter removal.
3. Regarding membrane function, which of the following statements
is/are false?
A. Regular use of hypertonic glucose exchanges is associated with
an increased risk for acquired membrane injury.
B. There should be a minimum target of 1 liter of ultrafiltration
(UF) per day.
C. Rapid solute transport contributes to poor UF but can be addressed
by use of APD and icodextrin such that it no longer is associated
with increased mortality.
D. Routine computed tomography (CT) scanning to look for pro-
gressive membrane thickening and calcification is the best way
to screen for encapsulating peritoneal sclerosis (EPS).
E. Progressive loss of osmotic conductance is thought to represent
increasing fibrotic damage, may predispose to EPS, and is a reason
for switching to hemodialysis.